TW201816002A - Colored hydrogel contact lenses with lubricious coating thereon - Google Patents

Abstract

The invention is generally related to colored contact lenses which comprise a hydrogel lens body having an opaque color image therein and/or thereon and a durable lubricious coating thereon. The coating comprises an anchoring layer of a polyanionic polymer having carboxyl groups and a hydrogel layer which is derived from a hydrophilic polymeric material having azetidinium groups and is covalently attached onto the anchoring layer of the polyanionic polymer through linkages each formed between one carboxyl group and one azetidinium groups. The colored contact lens has a surface lubricity better than the lubricity of the non-silicone hydrogel lens body and a friction rating of about 2 or lower after 7 cycles of manual rubbing.

Description

   Colored hydrogel contact lens with lubricating coating thereon   

The present invention relates to colored hydrogel contact lenses which have a soft lubricating hydrogel coating thereon. In addition, the present invention provides a method for making such a colored hydrogel contact lens.

Colored contact lenses have been used to modify or enhance the color of the wearer's eyes. In general, there are two types of colored contact lenses. The first type of colored contact lenses are those that use substantially transparent enhanced colors that are combined with the colors of the natural iris to create a new look. Such tinted lenses are typically used to turn hazel eyes into light green colored eyes. These colored lenses may not turn the dark brown iris underneath into blue. The second category is a type of opaque colored lens having a continuous opaque pattern that completely covers the iris or an intermittent opaque pattern that partially covers the iris. Opaque colored contact lenses can effectively and significantly modify the eye color of the wearer.

Opaque colored contact lenses that can provide a natural appearance can be produced by printing a colored image directly onto the surface of a preformed contact lens with an ink including pigment particles. However, opaque colored contact lenses made according to this technology may have pigment particles protruding outward from the lens surface and may impart discomfort when worn by a user.

In order to reduce such wearing discomfort, opaque colored contact lenses can be advantageously produced by first printing a colored image with a pigment-containing ink on the molding surface of a mold for casting molding of contact lenses, The forming composition is distributed in a mold having a colored image printed on one of the molding surfaces, and the lens forming composition is cured to obtain a cast-molded contact lens having the printed colored image, where the curing is performed. The printed colored image is transferred from the molding surface to the cast-molded contact lens during the process. Although an opaque colored contact lens made according to this technology may have pigment particles embedded in the lens surface but still exposed (ie, not protruding outward from the lens surface), the surface of the opaque colored contact lens The printed areas (i.e., particle-exposed areas) will have a much higher roughness than the non-printed areas. Higher roughness in printed areas on the lens surface may still impart discomfort to wearing.

In order to reduce the roughness, it has been proposed to apply a clear coating (that is, a layer of a polymerizable composition that can be a lens-forming composition or any polymerizable composition that does not contain any colorants to the molding surface of the mold) and use A pigmented ink prints a colored image onto a clear coating on the molded surface. However, due to the loss of print strength and increased smearing effects, print quality may be severely degraded by the clear coating.

Therefore, there is still a need for a process for producing opaque colored contact lenses and such opaque colored contact lenses, which can provide users with enhanced wearing comfort.

In one aspect, the present invention provides a method for producing a soft contact lens, the method comprising the following steps: (1) obtaining a prefabricated hydrogel contact lens having a front surface and a rear surface of the hydrogel contact lens; A color image printed with an ink in and / or on one of the surfaces, wherein the ink contains pigment particles and optionally one or more dyes; (2) contacting the prefabricated hydrogel with a lens at a pH of about 4.0 or less And an aqueous solution of a first coating of a polyanionic polymer at a coating temperature of from about 25 ° C to about 80 ° C to obtain a colored contact lens precursor having the color image and the poly The prefabricated hydrogel contact lens of a layer of an anionic polymer, wherein the polyanionic polymer is a homopolymer or copolymer of one or more acrylic, methacrylic, or ethacrylic acids, wherein the layer of the polyanionic polymer Encapsulating the prefabricated hydrogel contact lens having the color image; and (3) pre-characterizing the colored contact lens obtained in step (2) in a water-soluble and heat-crosslinkable material having a tetrahydroazine group Linked Pro The second coating aqueous solution of the polymer material is heated at a temperature from about 60 ° C. to about 140 ° C. for at least 30 minutes to cross-link the water-soluble heat-crosslinkable hydrophilic polymer material and the polyanionic polymerization. In order to form the colored contact lens with a hydrogel coating covalently attached to the layer of the polyanionic polymer, wherein the colored contact lens in a fully hydrated state has between 7 A friction level of about 2 or less after cyclic manual friction.

In another aspect, the present invention provides a colored hydrogel contact lens comprising: a hydrogel lens body having an opaque color image thereon and / or therein; and a coating, the A coating encapsulates the hydrogel lens body and the opaque color image, wherein the coating comprises an anchor layer of a polyanionic polymer and a layer of a hydrogel material, wherein the polyanionic polymer is one or more acrylic, methyl Homopolymer or copolymer of methacrylic acid, ethacrylic acid, or 2- (meth) acrylamidoglycolic acid, wherein the hydrogel material is derived from a water-soluble, heat-crosslinkable compound having a tetrahydroazinonium group And a covalently attached hydrophilic polymer material and are covalently attached to the anchor layer of the polyanionic polymer by a bond each formed between a carboxyl group and a tetrahydroazine group. Colored contact lenses in a hydrated state have about 2 or less after 7 cycles of manual rubbing (preferably about 1.5 or less, more preferably about 1.0 or less, even more preferably about 0.5 or lower).

FIG. 1 shows the total liquid coverage as a function of time for a control lens and a colored contact lens of the present invention according to a preferred embodiment.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature and laboratory procedures used herein are well known and commonly used in the art. Conventional methods are used for such procedures, such as those provided in the art and various general references. When providing a term in the singular, the inventors also considered the plural of the term. The nomenclature used herein and the laboratory procedures described below are those well known and commonly used in the art.

As used herein, "about" refers to a number referred to as "about" that includes the recited number plus or minus 1% -10% of that recited number.

"Conditional" or "Conditional" means that the event or situation described later may or may not occur, and that the description includes situations in which the event or situation occurs and situations in which it does not occur.

"Contact lens" refers to a structure that can be placed on or inside the wearer's eyes. Contact lenses can correct, improve, or change a user's vision, but they do not have to. The contact lens may have any suitable material known in the art or later developed, and may be a soft lens, a rigid lens, or a hybrid lens. A "non-silicone hydrogel contact lens" refers to a contact lens that includes a non-silicone hydrogel body (core) material. The "silicone hydrogel contact lens" refers to a contact lens including a silicone hydrogel body (core) material.

The "soft contact lens" refers to a contact lens having an elastic modulus (ie, Young's modulus) of less than 2.0 MPa (preferably less than 1.5 MPa, more preferably less than 1.0 MPa).

A "hydrogel" or "hydrogel material" refers to a crosslinked polymer material that has a three-dimensional polymer network (ie, a polymer matrix), is insoluble in water, but can polymerize when it is fully hydrated The substrate retains at least 10% water by weight.

As used herein, the term "non-silicone hydrogel" refers to a hydrogel that is theoretically free of silicon.

"Silicone hydrogel" refers to a silicone-containing hydrogel obtained by copolymerization of a polymerizable composition that contains at least one silicone-containing monomer or at least one silicone-containing macromolecule. Monomer or at least one crosslinkable silicone-containing prepolymer.

As used herein, the "front surface or front surface" of a contact lens refers to the surface of the lens that faces away from the eye during wearing. The generally convex front surface may also be referred to as the front curved surface of the lens.

As used herein, the "back surface or rear surface" of a contact lens refers to the surface of the lens that faces the eye during wear. The generally concave rear surface may also be referred to as the base curve of the lens.

"Colored contact lens" means a contact lens (hard or soft) with a colored image printed on and / or in it. The color image may be a cosmetic pattern (eg, an iris pattern), a Wild Eye ^™ pattern, a custom-made (MTO) pattern, and the like. The color image may be a monochrome image or a polychromatic image.

The term "light-transmitting" as used herein is intended to describe a transparent or translucent color or a portion of a lens that is uncolored or coated with a transparent or translucent color.

"Pigment" means a powdery substance suspended in a liquid in which it is insoluble. Pigments are used to impart color. Pigments are generally less opaque than dyes.

As used herein, "surface hydrophilicity" describes a surface characteristic that represents the degree to which a surface interacts with water, as measured by Water Break Time (WBUT). The higher the WBUT value, the higher the surface hydrophilicity.

According to the present invention, the "surface lubricity" of a contact lens (or medical device) is measured by a friction level, which is a number from 0 to 4. The higher the value of the friction level, the lower the surface lubricity.

As used herein, "hydrophilic" describes a material or a portion thereof that will more easily associate with water than a lipid.

"Lens-forming material" or "lens-forming composition" interchangeably refers to a polymerizable composition that can be cured (i.e., polymerized and / or cross-linked) by thermal curing or photochemical (i.e., by photochemical radiation) to A crosslinked polymer was obtained.

As used herein, "actinically" with respect to the curing, crosslinking, or polymerization of a polymerizable composition, prepolymer, or material means by actinic radiation, such as, for example, UV / visible light irradiation, ionizing radiation (eg, γ-ray or X-ray radiation), microwave irradiation, etc. for curing (such as crosslinking and / or polymerization). Thermal or actinic curing methods are well known to those skilled in the art.

"Vinyl monomer" refers to a compound having a unique ethylenically unsaturated group.

The term "soluble" with respect to a compound or material in a solvent means that the compound or material is soluble in the solvent at room temperature (i.e., from about 20 ° C to about 30 ° C) to obtain a compound having at least about 0.05% by weight. Concentration of solution.

The term "insoluble" with respect to a compound or material in a solvent means that the compound or material is soluble in the solvent at room temperature (as defined above) to obtain a solution having a concentration of less than 0.005% by weight.

The term "ethylenically unsaturated group" is used herein in a broad sense and is intended to encompass any group containing at least one> C = C <group. Exemplary ethylenically unsaturated groups include, but are not limited to, (meth) acrylfluorenyl ( and / or ), Allyl, vinyl (-CH = CH ₂ ), 1-methyl vinyl ( ), Styryl, or the like.

The term "(meth) acrylamide" refers to methacrylamide and / or acrylamide.

The term "(meth) acrylate" refers to methacrylate and / or acrylate.

As used herein, "hydrophilic vinyl monomer" refers to a vinyl monomer capable of polymerizing to form a water-soluble or homopolymer that can absorb at least 10 weight percent water.

"Hydrophobic vinyl monomer" refers to a vinyl monomer capable of polymerizing to form a homopolymer that is insoluble in water and can absorb less than 10 weight percent of water.

As used in this application, the term "molecular weight" of a polymeric material (including monomeric materials or macromonomer materials) refers to a weight average molecular weight (Mw), unless specifically stated otherwise or unless otherwise specified by the test conditions.

A "macromonomer" or "prepolymer" refers to a compound or polymer that contains ethylenically unsaturated groups and has a Mw greater than 700 Daltons.

As used herein, the term "vinyl crosslinker" refers to a compound having at least two ethylenically unsaturated groups. "Vinyl crosslinking agent" refers to a vinyl crosslinking agent having a Mw of about 700 Daltons or less.

As used herein, the term "polymer" means a material formed by polymerizing / crosslinking one or more monomers or macromonomers or prepolymers, or a combination thereof.

The term "alkyl" refers to a monovalent group obtained by removing a hydrogen atom from a linear or branched alkane compound. An alkyl group (group) forms a bond with one other group in an organic compound.

The terms "alkylene divalent group" or "alkylene diyl" or "alkyl diyl" interchangeably refer to a divalent group obtained by removing a hydrogen atom from an alkyl group. The alkylene divalent group forms two bonds with other groups in the organic compound.

The term "alkyltriyl" refers to a trivalent group obtained by removing two hydrogen atoms from an alkyl group. Alkyltriyl groups form three bonds with other groups in organic compounds.

The term "alkoxy or alkoxyl" refers to a monovalent group obtained by removing a hydrogen atom from a hydroxyl group of a linear or branched alkyl alcohol. An alkoxy group is a bond with one other group in an organic compound.

In this application, the term "substituted" with respect to an alkyldiyl or an alkyl group means that the alkyldiyl or the alkyl group includes at least one substituent, the at least one substituent replacing the alkyldiyl Or a hydrogen atom of the alkyl group, and is selected from the group consisting of: hydroxyl (-OH), carboxyl (-COOH), -NH ₂ , mercapto (-SH), C ₁ -C ₄ alkane group, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylthio (sulfide group), C ₁ -C ₄ acyl group, C ₁ -C ₄ alkylamino, di -C ₁ -C ₄ alkylamino, a halogen atom (Br or Cl), and combinations thereof.

In this application, " "Oxazoline" means Compounds, wherein: R ¹ is hydrogen, methyl, ethyl, N-pyrrolidinylmethyl, N-pyrrolidinylethyl, N-pyrrolidinylpropyl, or -alk- (OC ₂ H ₄ ) _m3 -OR "is a monovalent group, wherein alk is a C ₁ -C ₄ alkyl diradical; R" is a C ₁ -C ₄ alkyl (preferably methyl); and m3 is from 1 to 10 ( An integer of 1 to 5) is preferred.

In this application, the term "poly "Oxazoline" means having A linear polymer of the formula: T ₁ and T ₂ are two end groups; R ¹ is hydrogen, methyl, ethyl, N-pyrrolidinylmethyl, N-pyrrolidinylethyl, N-pyrrole Pyridylpropyl, or -alk- (OC ₂ H ₄ ) _m3 -OR "monovalent group, where alk is C ₁ -C ₄ alkyldiyl; R" is C ₁ -C ₄ alkyl (preferably Is methyl); m3 is an integer from 1 to 10 (preferably 1 to 5); x is an integer from 5 to 500. Gather The oxazoline segment has the chemical formula: A bivalent polymer chain in which R ¹ and x are as defined above.

In this application, the term "poly (2- Oxazoline-co-ethyleneimine) "means a statistical copolymer which has Chemical formula, wherein: T ₁ and T ₂ are end groups; R ¹ is hydrogen, methyl, ethyl, N-pyrrolidinylmethyl, N-pyrrolidinylethyl, N-pyrrolidinylpropyl, or -alk- (OC ₂ H ₄ ) _m3 -OR "is a monovalent group, wherein alk is C ₁ -C ₄ alkyldiyl; R" is C ₁ -C ₄ alkyl (preferably methyl); m3 is an integer from 1 to 10 (preferably 1 to 5); x is an integer from 5 to 500; z is an integer equal to or less than x. Poly (2- Oxazoline-co-ethyleneimine) Oxazoline is obtained.

In this application, the term "poly (2- "Azoline-co-ethyleneimine) -epichlorohydrin" means that by poly (2- Oxazoline-co-ethyleneimine) reacts with epichlorohydrin to convert poly (2- All or a large percentage of oxazoline-co-ethyleneimine ( 90%) of a polymer obtained by converting a secondary amine group into a tetrahydroazetidinium group. Poly (2- An example of an oxazoline-co-ethyleneimine) -epichlorohydrin is disclosed in U.S. Patent Application Publication No. 2016/0061995 A1 (herein incorporated by reference in its entirety).

"Epichlorohydrin-functional polyamine" or "epichlorohydrin-functional polyamine" refers to the polyamine or polyamine by reacting the polyamine or polyamine with epichlorohydrin. A polymer obtained by converting all or a large percentage of the secondary amine groups into tetrahydroazepine groups.

The term "polyamidoamine-epichlorohydrin" refers to an epichlorohydrin-functional adipic acid-diethylenetriamine copolymer.

In the present application, the term "tetrahydroazine" or "3-hydroxytetrahydroazine" refers to A positively charged divalent group (or group or moiety).

The term "thermally crosslinkable" with respect to a polymer material or functional group means that the polymer material or the functional group can be subjected to contact with another material or functional group at a relatively elevated temperature (from about 40 ° C to about 140 ° C). Cross-linking (or coupling) reaction, however, the polymer material or functional group is at room temperature (ie, from about 22 ° C to about 28 ° C, preferably from about 24 ° C to about 26 ° C, especially at about 25 ° C) Not able to withstand the same crosslinking reaction (or coupling reaction) as another material or functional group to the extent that it is detectable for a time of about one hour.

As used herein, the term "phosphocholine" refers to Monovalent zwitterionic radical, wherein the integer t1 lines 1 to 5 and R ₁ ", R _2" and R ₃ "independently of one another C ₁ -C ₈ lines alkyl or C ₁ -C ₈ hydroxyalkyl.

As used herein, the term "reactive vinyl monomer" refers to any vinyl monomer having at least one reactive functional group selected from the group consisting of a carboxyl group, a primary amine group, and Secondary amine group.

As used herein, the term "non-reactive vinyl monomer" means free of carboxyl groups, primary amine groups, secondary amine groups, epoxide groups, isocyanate groups, azlactone groups, Or any vinyl monomer (hydrophilic or hydrophobic vinyl monomer) of an aziridine group.

The free radical initiator may be a photo initiator or a thermal initiator. "Photoinitiator" refers to a chemical that initiates a free-radical crosslinking / polymerization reaction by using light. "Thermal initiator" refers to a chemical that initiates free-radical crosslinking and / or polymerization by using thermal energy.

"Spatial confinement of actinic radiation" refers to where energy radiation in the form of rays is directed by, for example, a mask or mask or a combination thereof in order to impinge on a region with a well-defined peripheral boundary in a space-limited manner. Behavior or process. The spatial limitation of UV radiation is obtained through the use of a mask or barrier having an area where radiation (e.g. UV and / or visible light) is transmissive, and radiation (e.g. UV and / or visible light) surrounding the area where the radiation is transmissive ) Impermeable area, and the projected outline of the boundary between the radio-opaque and radio-permeable areas, such as in U.S. Patent Nos. 6,800,225 (Figure 1-11), and 6,627,124 (Figure 1-9), 7,384,590 (Figures 1-6) and 7,387,759 (Figures 1-6) are schematically shown in the drawings, all of which are incorporated by reference in their entirety. The mask or barrier allows space to project a beam of radiation (eg, UV radiation and / or visible radiation) having a cross-sectional profile defined by the projection profile of the mask or screen. The beam of projected radiation (eg, UV radiation and / or visible radiation) limits the radiation impinging on the lens formulation in a projected beam path from the first molding surface to the second molding surface of the mold. The resulting contact lens includes a front surface defined by the first molding surface, an opposite rear surface defined by the second molding surface, and a lens edge defined by a cross-sectional profile of the projected UV and / or visible light beam (I.e., the spatial limitation of radiation). The radiant energy used for the crosslinking, especially UV radiation (and / or visible light radiation), gamma radiation, electronic radiation or thermal radiation, is preferably in the form of a substantially parallel beam, so that On the one hand good restrictions are achieved and on the other hand this energy is effectively used.

The term "modulus" or "elastic modulus" in relation to a contact lens or material means a tensile modulus or a Young's modulus as a stiffness measure of the contact lens or material. This modulus can be measured using the method according to the ANSI Z80.20 standard. Those skilled in the art are familiar with determining the elastic modulus of silicone hydrogel materials or contact lenses. For example, all commercial contact lenses have reported values of elastic modulus.

"Water contact angle" refers to the average water contact angle at room temperature obtained by averaging the contact angle measurements of at least 3 individual contact lenses (that is, the contact angle measured by the lie-down method) .

The term "durability" with respect to the coating on a hydrogel contact lens is intended to describe that the coating on a hydrogel contact lens can withstand a desired number of cycles of manual friction.

As used herein, "number of (" j ") cycles of manual rubbing" with respect to a coating on a contact lens means after j cycles of manual rubbing according to the procedure described in Example 1, the a contact lens having about 60% or less (preferably about 50% or less, more preferably about 40% or less, and even more preferably about 30% or less) in the j Increase in friction level caused by cyclic manual friction (ΔFR _DR ( j )), where , Where FR _0DR is the friction level of the contact lens in a fully hydrated state and has been subjected to zero manual friction, and FR _jDR is the friction level of the contact lens in a completely hydrated state and has been subjected to j cycles of manual friction, where j An integer of 2 (preferably 7, more preferably 14, even more preferably 30).

The term "one cycle of manual rubbing" means manually rubbing a contact lens (or medical device) with a coating thereon with a RENU® multifunctional lens care solution (or another multifunctional lens care solution) (wearing a disposable Powder latex gloves) for 20 seconds and then rinsed with saline. The above procedure can be repeated a given number of times, for example from 2 to 30 times, and the repeating number of manual friction is the number of cycles of manual friction.

"Aqueous solution" or "water-based solution" interchangeably refers to a solution that is a homogeneous mixture of a water-based solvent and one or more solutes dissolved in the water-based solvent. "Water-based solvent" is intended to describe a solvent system that is at least 70% by weight (preferably at least 80%, more preferably at least 90%, or even more) relative to the weight of the solvent system. More preferred is at least 95%) water and up to 30% by weight (preferably about 20% or less, more preferably about 10% or less, even more preferably about 5%). % Or less, especially about 2% or less) of one or more organic solvents. The coating aqueous solution refers to an aqueous solution containing at least one polymer coating material as a solute in a solution.

"Organic-based solution" refers to a solution that is a homogeneous mixture consisting of an organic-based solvent and one or more solutes dissolved in the organic-based solvent. "Organic-based solvent" is intended to describe a solvent system consisting of one or more organic solvents and less than 40% by weight, preferably about 30% or less, relative to the weight of the solvent system, More preferred is a water composition of about 20% or less, even more preferably about 10% or less, especially about 5% or less. The organic-based coating solution refers to an organic-based solution containing at least one polymer coating material as a solute in the solution.

"Printing process on a mold for producing colored contact lenses" refers to a method for molding colored contact lenses described in Rawlings et al., U.S. Patent No. 5,034,166 (incorporated herein by reference). process.

The present invention generally relates to a method for producing colored contact lenses that are designed to enhance the eye color of a wearer while providing a very natural appearance as perceived by ordinary observation. The colored contact lens of the present invention includes a hydrogel lens body, a colored image printed on or on the surface of the hydrogel lens body, and a coating on the surface of the hydrogel lens body. The coating has a thickness of at least 0.1 μm and includes an anchor layer of a polyanionic polymer having a carboxyl group and a soft lubricated hydrogel layer covalently attached to the anchor layer. With a relatively thick layer of a soft lubricated hydrogel layer on this surface, the colored contact lens can provide superior wearing comfort over currently available commercial colored contact lenses.

It was found that such colored contact lenses can be produced by applying a soft lubricating hydrogel coating according to a simple solution coating process. To form such a coating, a water-based coating process can be used to apply an anchor layer of a polyanionic polymer (e.g., polyacrylic acid or polymethacrylic acid or the like) to a pre-formed colored contact lens that The lens has a color image printed in or on at least one of the lens surfaces (front or back surface). It is believed that functional groups (e.g., amido, hydroxyl, polyethylene glycol segments, or the like) of the lens hydrogel material with the polyanionic polymer at low pH (i.e., less than about 4.0) The hydrogen bonds formed between the carboxyl groups (in protonated form) may be sufficient to allow the hydrogel contact lens to stably bind the layer of the polyanionic polymer. Such a layer of the polyanionic polymer can completely cover the surface of the hydrogel contact lens, even pigment particles protruding from the lens surface or a printed area in the lens surface, even though the pigment particles may not contain A functional group that forms a hydrogen bond with the polyanionic polymer. Such a layer of a polyanionic polymer can function as an anchoring layer for covalently attaching the hydrogel layer to form a relatively durable lubricious coating having a desired thickness. It was further found that the obtained colored contact lens has good surface lubricity and a lower elastic modulus than the elastic modulus of the lens body, thereby giving significantly improved wearing comfort.

In one aspect, the present invention provides a method for producing a soft contact lens, the method comprising the following steps: (1) obtaining a prefabricated hydrogel contact lens having a front surface and a rear surface of the hydrogel contact lens; A color image printed with an ink in and / or on one of the surfaces, wherein the ink contains pigment particles; (2) contacting the prefabricated hydrogel with a lens at about 4.0 or less (preferably about 3.5 or less) Small, more preferably about 3.0 or less, even more preferably from about 0.5 to about 2.5) and at a temperature from about 25 ° C to about 80 ° C (preferably from about 30 ° C to about The first aqueous solution of the polyanionic polymer at a coating temperature of 75 ° C, more preferably from about 35 ° C to about 70 ° C, and even more preferably from about 40 ° C to about 60 ° C) is contacted to A colored contact lens precursor is obtained, the precursor being the prefabricated hydrogel contact lens having the color image and a layer of the polyanionic polymer thereon, wherein the polyanionic polymer is one or more acrylic acid, methacrylic acid , Ethacrylic acid, or homopolymer of 2- (meth) acrylamidoglycolic acid Wherein the layer of the polyanionic polymer encapsulates the prefabricated hydrogel contact lens having the color image; and (3) the colored contact lens precursor obtained in step (2) is contained in a layer containing a tetrahydroazine group The water-soluble and heat-crosslinkable hydrophilic polymer material in the second coating aqueous solution is heated at a temperature from about 60 ° C to about 140 ° C for at least 30 minutes to crosslink the water-soluble heat-crosslinkable. A hydrophilic polymer material and the polyanionic polymer to form the colored contact lens with a hydrogel coating, the hydrogel coating being covalently attached to a layer of the polyanionic polymer, wherein the The fully hydrated colored contact lens has about 2 or less after 7 cycles of manual rubbing (preferably about 1.5 or less, more preferably about 1.0 or less, even more preferably (About 0.5 or less). Preferably, the elastic modulus of the colored contact lens is equal to the prefabricated water within a margin of about ± 10% or less (preferably about ± 8%, even more preferably about ± 6%). Modulus of elasticity of a gel contact lens.

According to the present invention, a prefabricated hydrogel contact lens is any hydrogel contact lens that is produced according to any lens manufacturing process and has not been subjected to any surface treatment after the lens formation process. For example, prefabricated contact lenses can be produced by conventional "rotary casting molding" as described, for example, in U.S. Patent No. 3,408,429, or by as described in U.S. Patent Nos. 4,347,198; 5,508,317; 5,583,463; 5,789,464; and 5,849,810 The all-cast molding method is produced in a static form, or by lathe cutting of buttons as used in making custom contact lenses. In casting molding, the lens formulation is typically dispensed into a mold and cured (ie, polymerized and / or crosslinked) in the mold used to make the contact lens.

To produce prefabricated non-silicone hydrogel contact lenses, hydrogel lens formulations are typically: or (1) a monomer mixture comprising (a) at least one hydrophilic vinyl monomer (e.g., hydroxyl Ethyl methacrylate, glyceryl methacrylate, N-vinylpyrrolidone or a combination thereof) and (b) at least one component selected from the group consisting of: a crosslinking agent , Hydrophobic vinyl monomers, lubricants (or so-called internal wetting agents incorporated into lens formulations), free radical initiators (photoinitiators or thermal initiators), ultraviolet absorbers, visible colorants ( For example, dyes, pigments, or mixtures thereof), antimicrobial agents (for example, silver nanoparticle is preferred), bioactive agents, and combinations thereof; or (2) one or more water-soluble prepolymers and at least one selected An aqueous solution of the components of the group consisting of: hydrophilic vinyl monomers, crosslinkers, hydrophobic vinyl monomers, lubricants (or so-called internal lubricants incorporated into lens formulations) Aerosol), free radical initiator (photo or thermal initiator), Ultraviolet absorbing agent, a visibility tinting agent (e.g., dyes, pigments or mixtures thereof), antimicrobial agents (e.g., preferably silver nanoparticles), bioactive agents, and combinations thereof. The resulting prefabricated hydrogel contact lens can then be subjected to extraction with an extraction solvent to remove unpolymerized components from the resulting lens and to undergo a hydration process, as known to those skilled in the art. It should be understood that the presence of a lubricant in a hydrogel lens formulation improves the lubrication of a preformed hydrogel contact lens compared to a control prefabricated hydrogel contact lens obtained from a control hydrogel lens formulation without a lubricant Sex.

Currently, most commercially available non-silicone hydrogel contact lenses consist of a copolymer of hydroxyethyl (meth) acrylate and one or more vinyl monomers and one or more vinyl crosslinkers, glycerol (methyl ) Copolymer of acrylate with one or more vinyl monomers and one or more vinyl cross-linking agents, cross-linked polyvinyl alcohol.

To produce pre-made silicone hydrogel (SiHy) contact lenses, SiHy lens formulations for casting or spin casting molding or for preparing SiHy rods for use in lathe cutting of contact lenses generally include at least one A component selected from the group consisting of a silicone-containing vinyl monomer, a silicone-containing vinyl macromer, a silicone-containing prepolymer, and a hydrophilic vinyl monomer , Hydrophobic vinyl monomers, crosslinkers (compounds having a molecular weight of about 700 Daltons or less and containing at least two ethylenically unsaturated groups), free radical initiators (photoinitiators or thermal initiators) ), Hydrophilic vinyl macromonomers / prepolymers, and combinations thereof, as is well known to those skilled in the art. SiHy contact lens formulations may also include other necessary components known to those skilled in the art, such as, for example, ultraviolet absorbers, visibility colorants (e.g., dyes, pigments, or mixtures thereof), antimicrobials (e.g., Preferred are silver nano particles), bioactive agents, lubricants (or so-called internal wetting agents incorporated into lens formulations), leachable tear stabilizers and mixtures thereof, as known to those skilled in the art of. The resulting preformed SiHy contact lens can then be subjected to extraction with an extraction solvent to remove unpolymerized components from the resulting lens and to undergo a hydration process, as known to those skilled in the art.

Various SiHy lens formulations have been described in many patents and patent applications published since the filing date of this application. All of them can be used to obtain pre-made SiHy lenses. SiHy lens formulations for the preparation of commercial SiHy lenses (e.g. lotrafilcon A, lotrafilcon B, balafilcon A, galiltilcon A, senotilcon A, narafilcon A, narafilcon B, comfilcon A, enfilcon A, asmofilcon A, somofilcon A, stenfilcon A, smafilcon A, enfilcon A, and efrofilcon A) can also be used to make prefabricated SiHy contact lenses.

Lens molds for making contact lenses are well known to those skilled in the art and are used, for example, in casting molding or rotary casting. For example, a mold (for casting molding) typically includes at least two mold areas (or portions) or mold halves, ie, first and second mold halves. The first mold half defines a first molding (or optical) surface and the second mold half defines a second molding (or optical) surface. The first and second mold halves are configured to receive each other such that a lens-forming cavity is formed between the first molding surface and the second molding surface. The mold surface of the mold half is the cavity-forming surface of the mold and is in direct contact with the lens-forming material.

Methods of making mold areas for casting molded contact lenses are generally well known to those skilled in the art. The method of the present invention is not limited to any particular method for forming a mold. In fact, any mold forming method can be used in the present invention. The first and second mold halves can be formed by various techniques such as injection molding or lathe processing. Examples of suitable processes for forming a mold half are disclosed in U.S. Patent Nos. 4444711, 4460534, 5843346, and 5894002, which are also incorporated herein by reference.

Almost all materials known in the art for making molds can be used to make molds for making contact lenses. For example, polymer materials such as polyethylene, polypropylene, polystyrene, PMMA, Topas® COC grade 8007-S10 (from Frankfurt, Germany and Summit, New Jersey, USA) Ticona GmbH (a transparent amorphous copolymer of ethylene and norbornene) and the like. Other materials that allow UV transmission, such as quartz glass and sapphire, can be used. Polar plastic molds may preferably be used to produce silicone hydrogel contact lenses with much better wetting properties than non-polar plastic molds (e.g., polypropylene molds) (see, Lai and Friends, "Surface Wettability Enhancement of Silicone Hydrogel Lenses by Processing with Polar Plastic Molds ", J. Biomea.Mat.Res. [Journal of Biomedical Materials Research] 35 ( 3): 349-356 (1997); U.S. Patent No. 5,352,714, incorporated herein by reference in its entirety).

Reusable molds can also be used and the lens formulations can be actinically cured under the spatial constraints of actinic radiation to form contact lenses. Examples of preferred reusable molds are those disclosed in U.S. Pat. Nos. 6,800,225, 7,384,590, and 7,387,759, which are incorporated by reference in their entirety. Reusable molds can be made of quartz, glass, sapphire, CaF ₂ , cycloolefin copolymers (e.g., ^{Topas from} Ticona GmbH of Frankfurt, Germany and Summit, New Jersey) ® COC grade 8007-S10 (a transparent amorphous copolymer of ethylene and norbornene), Zeonex® and Zeonor® from Zeon Chemicals LP, Louisville, KY), Made of polymethyl methacrylate (PMMA), polyformaldehyde (Delrin) from DuPont, Ultem® (polyethersulfonimide) from GE Plastics, PrimoSpire®, etc.

According to the present invention, the lens formulation can be introduced (dispensed) into a cavity formed by a mold according to any known method.

After the lens formulation is dispensed into a mold, it is polymerized to produce a contact lens. Polymerization may preferably be thermally or photoinitiated by exposing the lens formulation in the mold to the spatial constraints of actinic radiation to crosslink the polymerizable components in the lens formulation.

Opening the mold makes it possible to remove the molded object from the mold in a manner known per se.

Molded contact lenses can be subjected to lens extraction to remove unpolymerized polymerizable components. The extraction solvent may be any solvent known to those skilled in the art. Examples of suitable extraction solvents are those described above.

In a preferred embodiment, the prefabricated hydrogel contact lens is a non-silicone hydrogel composed of a polymer comprising at least 50% by mole of repeating units of one or more hydroxyl-containing vinyl monomers. Contact lenses. Those skilled in the art know that vinyl monomers containing hydroxyl groups are suitable for making hydrogel contact lenses. Examples of preferred hydroxyl-containing vinyl monomers include, but are not limited to, hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, 3-hydroxypropyl (meth) acrylate, glycerol (Meth) acrylate, N-2-hydroxyethyl (meth) acrylamide, N-2-hydroxypropyl (meth) acrylamide, N-3-hydroxypropyl (meth) acrylamine Amine, N, N-bis (hydroxyethyl) (meth) acrylamide, N-2,3-dihydroxypropyl (meth) acrylamide, N -tris (hydroxymethyl) methyl (methyl Group) acrylamide, vinyl alcohol, allyl alcohol, and combinations thereof. Optionally, but preferably, the pre-made non-silicone hydrogel contact lens is composed of a polymer containing at least 50% by mole of at least one repeating unit of a hydroxyl-containing vinyl monomer and at least one A repeating unit of a vinylamine-containing vinyl monomer. It is believed that the amido group in such a vinylamine-containing vinyl monomer can form a hydrogen bond with a carboxyl group. Examples of preferred vinylamine-containing vinyl monomers include, but are not limited to, (meth) acrylamide, N, N-dimethyl (meth) acrylamide, N-vinylpyrrolidone (NVP) , N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, N, N-dimethylaminopropyl (Meth) acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5- Methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3 -Methylene-2-pyrrolidone, and combinations thereof.

In another preferred embodiment, the prefabricated non-silicone hydrogel contact lens is a polyvinyl alcohol-based hydrogel contact lens. More preferably, the preformed polyvinyl alcohol-based hydrogel contact lens is obtained by polymerizing an aqueous lens forming composition containing a water-soluble, actinically crosslinkable polyvinyl alcohol prepolymer, the prepolymer comprising : Repeating unit of vinyl alcohol (ie, ); Having a repeating crosslinking unit of formula (I); and Wherein: R ₃ may be hydrogen or C ₁ -C ₆ alkyl (preferably hydrogen); R ₄ is a C ₁ -C ₆ alkylidene divalent group (preferably C ₁ -C ₄ alkyl) A divalent group, more preferably a methylene or butylene divalent group, and even more preferably a methylene divalent group); R ₅ is hydrogen or C ₁ -C ₆ alkyl (preferably Hydrogen or C ₁ -C ₄ alkyl, more preferably hydrogen or methyl or ethyl, even more preferably hydrogen or methyl); R ₆ series or Ethylenically unsaturated groups, wherein q1 and q2 are independently zero or 1 and R ₇ and R ₈ are independently C ₂ -C ₈ alkylene divalent groups, and R ₉ is C ₂ -C ₈ Alkenyl.

Preferably, wherein R ₄ is a methylene divalent group, R ₅ is hydrogen or C ₁ -C ₄ alkyl, R ₃ is hydrogen, and R ₆ is Group, wherein R ₉ q2 zero-based vinyl-based (* -CH = CH ₂₎ or 1-methyl-vinyl _{(* -C (CH 3) =} CH 2). More preferably, the polyvinyl alcohol prepolymer has a weight average molecular weight of at least about 2,000 Daltons, and comprises from about 1% to about 25% by mole, and more preferably from about 2 by mole % To about 15% have repeating units of formula (I). Water-soluble, actinically crosslinkable polyvinyl alcohol prepolymers can be prepared using techniques known in the art, such as described in U.S. Patent Nos. 5,583,163 and 6,303,687 (incorporated by reference in their entirety herein). Those ones.

In another preferred embodiment, the prefabricated hydrogel contact lens is a silicone hydrogel contact lens.

Those skilled in the art know how to obtain a prefabricated hydrogel contact lens having and / or having a color image in it according to any known method.

One of the well-known methods involves printing ink directly on at least one of the front and back surfaces of a preformed hydrogel contact lens according to pad printing and / or inkjet printing techniques.

Any ink can be used in the present invention. Generally, the ink contains pigment particles and at least one binder polymer and a solvent. It optionally includes a cross-linking agent, a wetting agent, a surfactant, a monomer, a polymerization initiator, an antimicrobial agent, an antioxidant, an antiscalant, and other additives known in the art.

"Binder polymer" refers to a cross-linkable polymer that includes cross-linkable groups and can be used by a cross-linking agent or when chemical or physical means (e.g., moisture, heating, UV radiation Etc.) can be crosslinked upon initiation to capture or bind colorants (ie, pigment particles) to or into contact lenses, such as items known in the art.

The term crosslinkable group is used in this broad sense and is intended to cover, for example, functional groups and photocrosslinkable or thermally crosslinkable groups well known to those skilled in the art. It is well known in the art that a pair of matched crosslinkable groups can form covalent bonds or linkages under known reaction conditions such as, for example, redox conditions, dehydration condensation conditions, addition conditions, substitution (substitution) conditions, freedom Radical polymerization conditions, 2 + 2 cycloaddition conditions, Diels-Alder reaction conditions, ROMP (ring-opening metathesis polymerization) conditions, curing conditions, cationic crosslinking conditions, and epoxy resin hardening conditions. For example, amine groups can be covalently bonded to aldehydes (the Schiff base formed from aldehyde groups and amine groups can be further reduced); hydroxyl and amine groups can be covalently bonded to carboxyl groups; carboxyl and sulfo groups can be Covalently bonded to a hydroxyl group; Mercapto group can be covalently bonded to an amine group; or Carbon-carbon double bond system can be covalently bonded to another carbon-carbon double bond.

Exemplary covalent bonds or linkages formed between multiple pairs of crosslinkable groups include, but are not limited to, alkanes (carbon-carbon single bonds), olefins (carbon-carbon double bonds), esters, ethers, acetals, ketals, Vinyl ether, carbamate, urea, amine, amidine, enamine, imine, oxime, amidine, imide, carbonate, orthoester, phosphonate, phosphinate, sulfonate , Sulfinate, sulfide, sulfate, disulfide, sulfenamide, sulfanilamide, thioester, aryl, silane, siloxane, heterocycle, thiocarbonate, thioaminomethyl Acid esters and phosphatidylamine.

Exemplary crosslinkable groups include, but are not limited to, hydroxyl, amine, amido, sulfhydryl, -COOR (R and R'-based hydrogen or C ₁ to C ₈ alkyl), halide (chloride, bromide , Iodide), chloro, isothiocyanate, isocyanate, trichloro Dichlorotri , Mono or dihalopyridine, mono or dihalo di , Phosphoramidite, maleimide, aziridine, sulfazone, hydroxysuccinimide, hydroxythiosuccinimide, imidate, hydrazine, azidonitrophenyl group , Azide, 3- (2-pyridyl) propanamide, glyoxal, aldehyde, epoxy resin, ethylenically unsaturated free radicals.

The binder polymer in the ink can be any polymer that is compatible with the lens material. Adhesive polymers can be made by containing vinyl alcohol, vinyl butyral, vinyl acetate, acrylic acid, methacrylic acid, hydroxyl C ₁ to C ₆ acrylic acid and alkyl methacrylate, amino C ₁ to C ₈ acrylic acid It is prepared by polymerization with monomers of alkyl methacrylate, acrylic acid and glyceryl methacrylate, vinyl pyrrolidone, vinyl chloride, hydroxyethyl methacrylate, dimethylacrylamide, and the like. Mixtures of these monomers can be made to form many different copolymers. Other copolymers may include a variety of different cellulose resins, polyesters, polyurethanes, polyureas, or polyamides with at least one crosslinkable group. Preferably, the monomers used in preparing the adhesive polymer are the same as those used in making the lens.

The ink for printing the colored lenses of the present invention can be prepared according to any known suitable method. For example, a solution of a binder polymer and a solvent is first prepared and this solution is mixed with a paste containing a colorant to form an ink. It is currently preferred to form the ink from an adhesive polymer solution having a viscosity of about 40,000 cps.

Pad printing is known (e.g., see Spivak (Spivack) U.S. Patent No. 3,536,386 in the case of the present art; U.S. Patent Nos Knapp (Knapp) of 4,582,402 and 4,704,017; Rawlings (Rawlings) et al. US Patent No. 5,034,166, which is incorporated herein by reference in its entirety). The following are typical examples of this printing. The image is etched into the metal to form a lead plate. Place the lead plate in the printing press. Once in the printer, the lead plate is inked by an open ink pool scraping system or by a closed ink cup sliding on the image. Then, the silicone pad picks up the inked image from the lead plate and transfers the image to the contact lens. Silicone pads are made of a material that includes silicone that can vary in elasticity. The properties of the silicone material allow the ink to temporarily adhere to the pad and completely release the ink from the pad when it comes into contact with the lens or mold. Suitable pad printing structures include, but are not limited to, Tampo-type printing structures (Tampo vario 90/130), rubber stamps, thimbles, doctor blades, direct printing, or transfer printing, as they are known in the art.

Any known suitable silicone pad can be used in the present invention. Silicone pads are commercially available. However, different pads can give different printing qualities. Those skilled in the art will know how to choose a pad for a given ink.

Lead plates can be made of ceramic or metal (eg, steel). When the lead plate is made of steel, it will be desirable to neutralize the pH of the water-based ink by adding a buffer (for example, like phosphate) (for example, adjusting the pH to 6.8 to 7.8). The image can be etched into the cliche according to any method known to those skilled in the art, such as by chemical etching or laser ablation, and the like. It is also desirable to clean the lead plate after use using standard cleaning techniques known to those skilled in the art, such as, for example, immersion in solvents, sonic degradation, or mechanical abrasion.

It should be understood that the front (convex) surface or the rear (concave) surface of the lens can be printed, but it is currently preferred to print the front surface.

Printing lenses using inkjet printing processes is described in published US patent applications 2001/0050753, 2001/0085934, 2003/0119943, and 2003/0184710, which are incorporated herein by reference in their entirety.

Alternatively, a preformed water having a color image on it and / or having a color image therein can be made according to those similar on-die printing processes described in U.S. Patent No. 5,034,166 to Rawlings et al. (Incorporated herein by reference). The gel contacts the lens. The ink may be first applied to the molding surface of one or more mold parts by using pad printing (or transfer printing) or inkjet printing to form a colored coating (colored image). The colored coating can be applied on a molding surface that defines the rear (concave) surface of the contact lens or on a molding surface that defines the front (convex) surface of the contact lens or on both mold portions. Preferably, a colored coating (colored image) is applied on a molding surface that defines the front surface of the contact lens.

After the ink of the present invention is printed on a molding surface of a mold, the printed ink may be thermally or photocured. It is desirable to the extent that the printed ink is photochemically cured to minimize the loss of pattern sharpness of the color image produced by the subsequent filling lens forming material.

Many colored hydrogel contact lenses are commercially available. Those commercially available colored hydrogel contact lenses can be used in the present invention.

According to the present invention, the contact of the prefabricated hydrogel contact lens with the first coating aqueous solution may occur by dipping it into the first coating aqueous solution or by spraying it with the first coating aqueous solution. A contact process involves immersing the prefabricated hydrogel contact lens separately in a bath of an aqueous first coating solution for a period of time or alternatively immersing the prefabricated hydrogel contact lens sequentially in a series of first aqueous coating solutions. The bath lasts for a fixed, shorter period of time for each bath. Another contacting process involves spraying a first aqueous coating solution separately. However, many alternatives involve various combinations of spray- and dip-steps that can be designed by those skilled in the art. Preferably, the contacting step is performed by immersing the prefabricated hydrogel contact lens in the first coating aqueous solution.

The first coating aqueous solution has a pH of about 4 or less, preferably about 3.5 or less, more preferably about 3.0 or less, and even more preferably from about 0.5 to about 2.5.

The first coating aqueous solution has a temperature of from about 25 ° C to about 80 ° C (preferably from about 30 ° C to about 75 ° C, more preferably from about 35 ° C to about 70 ° C, even more preferably from About 40 ° C to about 60 ° C) (ie, coating temperature).

Contacting the prefabricated hydrogel contact lens with the first coating aqueous solution for at least about one minute, preferably at least about 5 minutes, more preferably at least about 10 minutes, and even more preferably about 30 minutes Contact time.

According to the present invention, the polyanionic polymer is a homopolymer or copolymer of one or more acrylic, methacrylic, or ethacrylic acid; preferably poly (acrylic acid) (PAA), poly (methacrylic acid) ( PMAA), poly (acrylic acid-co-methacrylic acid) (pAA-pMAA), poly (ethyl acrylic acid) (PEAA), poly (acrylic acid-co-ethyl acrylic acid) (pAA-pEAA), poly (methacrylic acid) -Co-ethylacrylic acid) (pMAA-pEAA), or a combination thereof; more preferred are poly (acrylic acid) (PAA), poly (methacrylic acid) (PMAA), poly (acrylic acid-co-methacrylic acid) (pAA-pMAA), or a combination thereof. The polyanionic polymer has at least 100,000 Daltons (preferably from 200,000 to 10,000,000 Daltons, more preferably from 300,000 to 5,000,000 Daltons, even more preferably from 400,000 to 3,000,000 Daltons. ) Weight average molecular weight.

According to the present invention, the water-soluble and heat-crosslinkable hydrophilic polymer material contains a tetrahydroazinonium group and is a cross-linking reaction shown in Scheme I. At least one polymer containing tetrahydroazinonium and at least Partial reaction product of a hydrophilicity enhancer (ie, wetting agent) having at least one carboxyl group, primary amine group, secondary amine group, or thiol group

Where X ₁ is -S- *, -OC (= O)-*, or -NR '-*, where R' is hydrogen or C ₁ -C ₄ unsubstituted or substituted alkyl group, and * represents Organic group.

Any suitable tetrahydroaziridinium-containing polymer can be used in the present invention. Examples of tetrahydroazinonium-containing polymers include, but are not limited to, epichlorohydrin-functional polyamines, homopolymers of tetrahydroazineium-containing vinyl monomers, tetrahydroazineium-containing vinyl monomers A copolymer of a polymer with one or more vinyl monomers.

Preferably, the polymer containing tetrahydroazepine is an epichlorohydrin-functional polyamine. Epichlorohydrin-functional polyamines can be obtained by reacting epichlorohydrin with a polyamine polymer or a polymer containing a secondary amine group. For example, poly (alkyleneimine) or poly (aminoamine) as a polycondensate derived from a polyamine and a dicarboxylic acid (e.g., adipic acid-diethylene triamine copolymer) can be combined with epichlorine Alcohols react to form an epichlorohydrin-functional polymer; a homo- or copolymer of a mono-alkylamino alkyl (meth) acrylate or a mono-alkylamino alkyl (meth) acrylamide It can also react with epichlorohydrin to form epichlorohydrin-functional polyamines; poly (2- An oxazoline-co-ethyleneimine) copolymer can be reacted with epichlorohydrin to form an epichlorohydrin-functional polyamine (i.e., poly (2- Oxazoline-co-ethyleneimine) -epichlorohydrin). The epichlorohydrin-functionalized reaction conditions for polyamines or polyamidoamine polymers are taught in EP1465931 (herein incorporated by reference in its entirety). Preferred epichlorohydrin-functional polyamine polyamidoamine-epichlorohydrin (PAE) or poly (2- Oxazoline-co-ethyleneimine) -epichlorohydrin.

Polyamide amine - epichlorohydrin commercially available, such as for example, Kymene® from Hercules, Inc. or Polycup ^® resin (epichlorohydrin-functionalized adipate - two projecting triamine copolymer).

Poly (2- The oxazoline-co-ethyleneimine) -epichlorohydrin can be prepared according to the procedure described in US Patent Application Publication No. US 2016/0061995 A1 (incorporated herein by reference in its entirety).

Homopolymers and copolymers of tetrahydroazineium-containing vinyl monomers can be obtained according to procedures in U.S. Patent Application Publication No. 2013 / 0337160A1 (hereby incorporated by reference in its entirety).

Any suitable hydrophilicity enhancer can be used in the present invention, so long as they are ophthalmically compatible and contain at least one primary or secondary amine group, at least one carboxyl group, and / or at least one thiol group.

A preferred class of hydrophilicity enhancers includes, but is not limited to, monosaccharides containing a primary amine group, a secondary amine group, a carboxyl group, or a thiol group (e.g., 3-amino-1,2-propanediol, 1-thiol glycerol , 5-keto-D-gluconic acid, galactosamine, glucosamine, galacturonic acid, gluconic acid, aminogluconic acid, mannosamine, glucuronic acid 1,4-lactone, sugar acid, especially Ketodeoxynonulosonic acid, N -methyl-D-glucosamine, 1-amino-1-deoxy-β-D-galactose, 1-amino-1-deoxysorbitol, 1 -Methylamino-1-deoxysorbitol, N-aminoethylgluconamide); disaccharides containing primary, secondary, carboxyl or thiol groups (e.g. cartilage Disaccharide sodium salt, bis (β-D-xylpyranosyl) amine, digalacturonic acid, heparin disaccharide, hyaluronic acid disaccharide, lactobionic acid); and containing primary amine groups, secondary amine groups , Carboxyl, or thiol-based oligosaccharides (eg, carboxymethyl-β-cyclodextrin sodium salt, trigalacturonic acid); and combinations thereof.

Another type of preferred hydrophilicity enhancer is a hydrophilic polymer having one or more (primary or secondary) amine, carboxyl and / or thiol groups. More preferably, the amine group (-NHR ', wherein R' is as defined above), the carboxyl group (-COOH) and / or the thiol group (-SH) group are in a hydrophilic polymer as a hydrophilicity enhancer The content in is based on the total weight of the hydrophilic polymer, less than about 40% by weight, preferably less than about 30%, more preferably less than about 20%, even more preferably less than about 10 %.

A preferred class of hydrophilicity enhancers are polysaccharides containing (primary or secondary) amine or carboxyl groups, such as, for example, carboxymethyl cellulose (having a carboxyl content of about 40% or less based on repeating units -[C ₆ H _10-m O ₅ (CH ₂ CO ₂ H) _m ]-is estimated, where m is 1 to 3), carboxyethyl cellulose (having a carboxyl content of about 36% or less, The carboxyl group content is estimated based on the composition of the repeating unit-[C ₆ H _10-m O ₅ (C ₂ H ₄ CO ₂ H) _m ]-, where m is 1 to 3), carboxypropyl cellulose (having about 32% or less carboxyl group content, which is estimated based on the composition of the repeating unit-[C ₆ H _10-m O ₅ (C ₃ H ₆ CO ₂ H) _m ]-, where m is 1 to 3) Hyaluronic acid (having a carboxyl content of about 11%, which is estimated based on the composition of repeating units-(C ₁₃ H ₂₀ O ₉ NCO ₂ H)-), chondroitin sulfate (having a carboxyl content of about 9.8% The content of the carboxyl group is estimated based on the composition of the repeating unit-(C ₁₂ H ₁₈ O ₁₃ NSCO ₂ H)-), or a combination thereof.

Another class of preferred hydrophilicity enhancers includes, but is not limited to, poly (ethylene glycol) (PEG) (e.g., PEG- NH ₂ , PEG-SH, PEG-COOH); H ₂ N-PEG-NH ₂ ; HOOC-PEG-COOH; HS-PEG-SH; H ₂ N-PEG-COOH; HOOC-PEG-SH; H ₂ N -PEG-SH; multi-armed PEG with one or more amine groups (primary or secondary amine groups), carboxyl or thiol groups; PEG-SH with one or more amine groups (primary or secondary amine groups) ), A PEG dendrimer having a carboxyl group or a thiol group; a diamine group (primary or secondary amine group) or a dicarboxyl-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer; Monoamine group (primary amine group or diamine group) of non-reactive hydrophilic vinyl monomer (any of those described above) or phosphatidylcholine-containing vinyl monomer (any of those described above) Grade amine group) or a monocarboxyl-terminated homopolymer or copolymer; as a copolymer of a polymerization product of a composition, the composition contains (1) about 60% by weight or less, and preferably by weight is From about 0.1% to about 30%, more Preferably from about 0.5% to about 20%, even more preferably from about 1% to about 15% of one or more reactive vinyl monomers and (2) at least one non-reactive hydrophilic vinyl monomer Body; and combinations thereof.

According to the present invention, the reactive vinyl monomer may be a carboxyl group-containing vinyl monomer (any of those preferred examples described above), a primary amine group-containing vinyl monomer (any of those preferred examples described above) ), Or a vinyl monomer containing a secondary amine group (any of those preferred examples described above).

More preferably, the hydrophilicity enhancer is PEG-NH ₂ ; PEG-SH; PEG-COOH; H ₂ N-PEG-NH ₂ ; HOOC-PEG-COOH; HS-PEG-SH; H ₂ N-PEG -COOH; HOOC-PEG-SH; H ₂ N-PEG-SH; multi-armed PEG with one or more amine, carboxyl, or thiol groups; with one or more amine, carboxyl, or thiol groups PEG dendrimer; monoamine-, monocarboxy-, diamino-, or dicarboxy-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer, the non-reactive hydrophilic vinyl The monomer is selected from the group consisting of (meth) acrylamide, N-vinylpyrrolidone (NVP), N-vinyl-N-methylacetamide, glycerol (meth) acrylic acid Ester, hydroxyethyl (meth) acrylate, N-hydroxyethyl (meth) acrylamide, N-hydroxypropyl (meth) acrylamide, C _{1 with} a weight average molecular weight of up to 400 Daltons -C ₄ -alkoxypolyethylene glycol (meth) acrylate, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2 -Pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, N, N-dimethylaminoethyl (meth) acrylate, N, N-di Aminoaminopropyl (meth) acrylamide, a vinyl monomer containing phosphinocholine, and a combination thereof; a copolymer, the copolymer being a polymerization product of a composition, the composition comprising (1) From about 0.1% to about 30% by weight, preferably from about 0.5% to about 20%, more preferably from about 1% to about 15% acrylic acid, C ₁ -C ₃ alkyl acrylic acid, olefin Propylamine and / or amine-C ₂ -C ₄ alkyl (meth) acrylate, and (2) at least one non-reactive hydrophilic vinyl monomer selected from the group consisting of A group consisting of acrylamide, N, N-dimethylacrylamide, N-vinylpyrrolidone, a vinyl monomer containing phosphinocholine, N-vinyl-N-formyl Acetylamine, glycerol (meth) acrylate, hydroxyethyl (meth) acrylate, N-hydroxyethyl (meth) acrylamide, C ₁ -C with weight average molecular weight up to 400 Daltons ₄ -alkoxypolyethylene glycol (meth) acrylate, vinyl alcohol, and combinations thereof.

Examples of preferred non-reactive vinylphosphonium choline-containing vinyl monomers include, but are not limited to, (meth) acryloxyethylphosphocholine (also known as MPC), or 2-((methyl ) Acryloxy) ethyl-2 '-(trimethylamino) ethyl phosphate), (meth) acryloxypropylphosphonium choline (also known as 3-((methyl) (Acrylic acid) propyl-2 '-(trimethylamino) ethyl phosphate), 4-((meth) acrylic acid) butyl-2'-(trimethylamino) ethyl Phosphoric acid ester, 2-[(meth) acrylamidoamino] ethyl-2 '-(trimethylamino) -ethylphosphate, 3-[(meth) acrylamido] propyl- 2 '-(trimethylamino) ethyl phosphate, 4-[(meth) acrylamido] butyl-2'-(trimethylamino) ethyl phosphate, 5-((methyl Propyl) propenyloxy) pentyl-2 '-(trimethylamino) ethyl phosphate, 6-((meth) propenyloxy) hexyl-2'-(trimethylamino)- Ethyl phosphate, 2-((meth) acryloxy) ethyl-2 '-(triethylamino) ethyl-phosphate, 2-((meth) acryloxy) ethyl -2 '-(tripropylamino) ethyl phosphate, 2-((meth) propenyloxy) ethyl-2'-(tributylamino) ethyl phosphate, 2-(( Propyl) propenyloxy) propyl-2 '-(trimethylamino) -ethyl phosphate, 2-((meth) propenyloxy) butyl-2'-(trimethylamino ) Ethyl phosphate, 2-((meth) acryloxy) pentyl-2 '-(trimethylamino) ethyl phosphate, 2-((meth) acryloxy) hexyl- 2 '-(trimethylamino) ethyl phosphate, 2- (vinyloxy) ethyl-2'-(trimethylamino) ethyl phosphate, 2- (allyloxy) ethyl -2 '-(trimethylamino) ethyl phosphate, 2- (vinyloxycarbonyl) ethyl-2'-(trimethylamino) ethyl phosphate, 2- (allyloxy Carbonyl) ethyl-2 '-(trimethylamino) -ethyl phosphate, 2- (vinylcarbonylamino) ethyl-2'-(trimethylamino) -ethyl phosphate, 2- (allyloxycarbonylamino) ethyl-2 '-(trimethylamino) ethyl phosphate, 2- (butenyloxy) ethyl-2'-(trimethylamino) ) Ethyl phosphates, those described in US Patent No. 5,461,433 (herein incorporated by reference in its entirety), and combinations thereof.

Most preferably, the hydrophilicity enhancer is PEG-NH ₂ ; PEG-SH; PEG-COOH; monoamine-, monocarboxy-, diamino-, or dicarboxy-terminated polyvinylpyrrolidone; Monoamine-, monocarboxy-, diamino-, or dicarboxy-terminated polypropylene amides; monoamine-, monocarboxy-, diamino-, or dicarboxy-terminated poly (DMA); monoamine Group- or monocarboxy-, diamino-, or dicarboxy-terminated poly (DMA-co-NVP); monoamino-, monocarboxy-, diamino-, or dicarboxy-terminated poly (NVP-co-NVP) -N, N-dimethylaminoethyl (meth) acrylate)); monoamine-, monocarboxy-, diamino-, or dicarboxy-terminated poly (vinyl alcohol); monoamine- , Monocarboxy-, diamino-, or dicarboxy-terminated poly [(meth) acryloxyethylphosphonium choline] homopolymer or copolymer; monoamine-, monocarboxy-, diamine Group- or dicarboxy-terminated poly (NVP-co-vinyl alcohol); monoamine-, monocarboxy-, diamino-, or dicarboxy-terminated poly (N, N-dimethylacrylamide- (Co-vinyl alcohol); poly [(meth) acrylic acid-co-acrylamido], having from about 0.1% to about 30% by weight, preferably from about 0.5% to about 2 0%, more preferably from about 1% to about 15% of (meth) acrylic acid; poly [(meth) acrylic acid-co-NVP], having from about 0.1% to about 30% by weight, (Meth) acrylic acid is preferably from about 0.5% to about 20%, more preferably from about 1% to about 15%; a copolymer, which is a polymerization product of a composition comprising (1 ) A vinyl monomer containing phosphatidylcholine, and (2) from about 0.1% to about 30% by weight, preferably from about 0.5% to about 20%, more preferably from about 1% Up to about 15% of acrylic acid, C ₁ -C ₃ alkylacrylic acid, allylamine, and / or amine-C ₂ -C ₄ alkyl (meth) acrylate; and combinations thereof.

Functional PEGs and multi-arm PEGs can be obtained from different commercial suppliers (eg, Polyscience, and Shearwater Polymers, inc., Etc.).

Monoamine, monocarboxy, diamine, or dicarboxy-terminated homopolymers or copolymers of one or more non-reactive hydrophilic vinyl monomers or a phosphinocholine-containing vinyl monomer may be Prepared by the procedure described in patent case number 6,218,508, which is incorporated herein by reference in its entirety. For example, in order to prepare a diamine or dicarboxy-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer, the non-reactive vinyl monomer, a chain transfer agent having a primary or secondary amine or carboxyl group (E.g., 2-aminoethanethiol, 2-mercaptopropionic acid, thioglycolic acid, thiolactic acid, or other hydroxythiols, aminothiols, or carboxyl-containing thiols) and optionally vinyl groups The monomer is copolymerized (thermally or actinically) with a reactive vinyl monomer (having a primary or secondary amine or carboxyl group) in the presence of a free radical initiator. In general, the molar ratio of the chain transfer agent to all vinyl monomers except the reactive vinyl monomer is from about 1: 5 to about 1: 100, and the Morse ratio is 1: 1. In this preparation, the chain transfer agent having a primary or secondary amine group or a carboxyl group is used to control the molecular weight of the produced hydrophilic polymer and form the ends of the produced hydrophilic polymer so as to provide one or two ends having one end. The resulting hydrophilic polymer with a secondary amine group or carboxyl group, and the reactive vinyl monomer provides another terminal carboxyl group or a primary or secondary amine group to the generated hydrophilic polymer. Similarly, in order to prepare a monoamine or monocarboxy-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer, the non-reactive vinyl monomer, a chain transfer having a primary or secondary amine or carboxyl Agents (e.g., 2-aminoethyl mercaptan, 2-mercaptopropionic acid, thioglycolic acid, thiolactic acid, or other hydroxythiols, aminothiols, or carboxyl-containing thiols) and optionally ethylene The base monomer is copolymerized (thermally or actinically) in the absence of any reactive vinyl monomer.

Includes non-reactive hydrophilic vinyl monomers and reactive vinyl monomers (eg, carboxyl-containing vinyl monomers, primary amine-containing vinyl monomers, or secondary amine-containing vinyl monomers) The copolymers can be prepared according to any well-known free-radical polymerization method or obtained from commercial suppliers. Copolymers containing methacryloxyethylphosphonium choline and carboxyl-containing vinyl monomers (or amine-containing vinyl monomers) are available from NOF (e.g. LIPIDURE®-A and -AF) .

The weight average molecular weight M _w of the hydrophilic polymer (as a hydrophilicity enhancer) having at least one amine group, carboxyl group, or thiol group is preferably from about 500 to about 5,000,000, and more preferably from about 1,000 to About 2,000,000, and even more preferably from about 5,000 to about 1,000,000 Daltons.

Water-soluble and heat-crosslinkable hydrophilic polymer materials can be used according to U.S. Patent Application Publication Nos. US 2016/0061995 A1 and US2013 / 0337160 A1 (herein incorporated by reference in their entirety) and U.S. Patent No. 8,529,057 ( Prepared by reference to the process disclosed in its entirety herein incorporated by reference.

In a preferred embodiment, the water-soluble heat-crosslinkable polymer material can be obtained by heating the aqueous reactive solution to a temperature from about 35 ° C to about 85 ° C and maintaining the temperature for a sufficient period of time. Time (about 6 hours or less, preferably about 5 hours, more preferably from about 2 hours to about 4 hours), the aqueous reactive solution comprises at least one polymer containing tetrahydroazine and At least one hydrophilicity enhancer (ie, wetting agent) having at least one reactive functional group selected from the group consisting of a primary amine group, a secondary amine group, a carboxyl group, a thiol group, And its combination. The aqueous reactive solution preferably contains one or more ionic compounds from about 70 mM to about 170 mM (preferably about 90 mM to about 150 mM, more preferably from about 100 mM to about 130 mM) and at least 8.0 (compared to Preferred is a pH of at least 8.5, more preferably at least 9.0, and even more preferably at least 9.5). It should be understood that the reaction time should be long enough to covalently attach the hydrophilic enhancer to the polymer chain of the tetrahydroazine-containing polymer, but should be short enough not to consume the tetrahydroazine All tetrahydroazinonium groups of the onium polymer and do not form a gel (i.e., not water soluble) (due to too much formation between the tetrahydroazinonium-containing polymer and the hydrophilicity enhancer The cross-bond). The resulting polymer material is a lightly crosslinked polymer material that has a highly branched structure and still contains thermally crosslinkable tetrahydroazinonium groups.

Those skilled in the art well understand how adjusting the pH of the reaction mixture, for example by adding a base _{(e.g., NaOH, KOH, NH 4 OH} , or mixtures thereof) or an acid _{(e.g., HCl, H 2 SO 4,} H 3 PO ₄ , citric acid, acetic acid, boric acid, or a mixture thereof).

According to the invention, any ionic compound can be used in the reactive mixture. Preferred ionic compounds are those used as ionic tonicity modifiers and ionic buffers used in ophthalmic solutions. Examples of preferred ionic tonicity modifiers include, but are not limited to, sodium chloride, potassium chloride, and combinations thereof. Examples of preferred ionic buffers include various salts of phosphoric acid (e.g. NaH ₂ PO ₄ , Na ₂ HPO ₄ , Na ₃ PO ₄ , KH ₂ PO ₄ , K ₂ HPO ₄ , K ₃ PO ₄ , or mixtures thereof), Various salts of boric acid (for example, sodium borate, potassium borate, or mixtures thereof), various salts of citric acid (for example, monosodium citrate, disodium citrate, trisodium citrate, monopotassium citrate, dipotassium citrate , Tripotassium citrate, or a mixture thereof), various salts of carbonic acid (for example, Na ₂ CO ₃ , NaHCO ₃ , K ₂ CO ₃ , KHCO ₃ , or a mixture thereof).

The aqueous reactive solution for preparing a water-soluble heat-crosslinkable polymer material can be prepared by: a desired amount of a polymer containing tetrahydroazine, and a desired amount of at least one kind of reactivity The functional group's hydrophilicity enhancer and the desired amount of other components (e.g., ion buffer, ion tension modifier, etc.) are dissolved in water (or a mixture of water and a small amount of a water-soluble organic solvent) to form an aqueous solution and then Adjust the pH of the aqueous solution (if necessary).

According to the present invention, the concentration ratio of the hydrophilicity enhancer in the aqueous reactive solution with respect to the polymer containing tetrahydroazine must be selected so that the obtained water-soluble heat-crosslinkable polymer material is insoluble in water (I.e., a solubility of less than 0.005 g / 100 ml of water at room temperature) and without consuming more than about 99%, preferably about 98%, more preferably about 97%, even more preferably about 96% of the tetrahydroazepine groups of the tetrahydroazepine polymer.

In a preferred embodiment, the aqueous reactive solution comprises from 0.01% to about 10% by weight (preferably from 0.05% to about 5% by weight, more preferably from 0.08 by weight). % To about 1%, even more preferably from 0.1% to about 0.4% by weight) of a polymer containing tetrahydroazine and from about 0.01% to about 10% by weight (preferably (From 0.02% to about 5% by weight, more preferably from 0.05% to about 2% by weight, even more preferably from 0.08% to about 1.0% by weight) has at least one reactivity Functional group (carboxyl group, primary amine group, secondary amine group) hydrophilicity enhancer, the concentration ratio of the tetrahydroazineium-containing polymer to the hydrophilicity enhancer is from about 1000: 1 to 1: 1000 (compared with It is preferably from about 500: 1 to about 1: 500, more preferably from about 250: 1 to about 1: 250, and even more preferably from about 100: 1 to about 1: 100).

In a preferred embodiment, the water-soluble heat-crosslinkable polymer material comprises (i) from about 20% to about 95% by weight derived from polyamidoamine-epichlorohydrin or poly (2- A first polymer chain of oxazoline-co-ethyleneimine) -epichlorohydrin, (ii) from about 5% to about 80% by weight of a hydrophilic moiety derived from at least one hydrophilicity enhancer or a second A polymer chain having at least one reactive functional group selected from the group consisting of a primary amine group, a secondary amine group, a carboxyl group, a thiol group, and a combination thereof (Preferably a carboxyl group), wherein the hydrophilic portion or the second polymer chain is separated by each of the polyamine-epichlorohydrin or the poly (2- One or more covalent bonds formed between an oxazoline-co-ethyleneimine) -epichlorohydrin and a tetrahydroazinonium group and an amine, carboxyl or thiol group of the hydrophilicity enhancer And covalently attached to the first polymer chains, and (iii) a tetrahydroazinonium group, which is part of the first polymer chains or is covalently attached to the first polymer chains Pendant or end groups on the polymer chain. The composition of the water-soluble, heat-crosslinkable polymer material is determined by the composition (based on the total weight of the reactants) of the reactant mixture used for such polymers according to the crosslinking reaction shown in Scheme I above. of. For example, if the reactant mixture includes about 75% polyamidoamine-epichlorohydrin and at least one hydrophilic enhancer by weight based on the total weight of the reactants (excluding solvents), the resulting chemistry The modified polyamidamine-epichlorohydrin includes about 75% by weight of a first polymer chain derived from polyamidamine-epichlorohydrin, and about 25% by weight of the first polymer chain. The hydrophilic portion of the hydrophilicity enhancer or the second polymer chain.

Preferably, the heating step is performed by autoclaving the colored contact lens precursor in the second coating aqueous solution at a temperature from about 115 ° C to about 125 ° C for about 20-90 minutes. The second coating aqueous solution is a packaging solution in a sealed lens package (ie, a buffered aqueous solution having a pH from 6.7 to 7.6). It is believed that those tetrahydroazinonium groups that are not involved in the crosslinking reaction can be hydrolyzed to 2,3-dihydroxypropyl (HO-CH ₂ -CH (OH) -CH _2- ) groups during autoclaving Tetrahydroazineium-containing polymer materials that are present in the lens packaging solution (if applicable) can be converted into non-reactive polymer wetting agents that improve lens insertion comfort. Therefore, the second aqueous coating solution is ophthalmologically safe after autoclaving.

Lens packages (or containers) are well known to those skilled in the art for autoclaving and storing soft contact lenses. Any lens package can be used in the present invention. Preferably, the lens package is a blister package comprising a substrate and a cover, wherein the cover is removably sealed to the substrate, wherein the substrate includes a cavity for receiving a sterile packaging solution and the contact lens.

The lenses are packaged in a separate package, sealed and sterilized (for example, by autoclaving under pressure at about 120 ° C or higher for at least 30 minutes) before dispensing to the user. Those skilled in the art should have a good understanding of how to seal and sterilize lens packaging.

According to the invention, the packaging solution contains at least one buffering agent and one or more other ingredients known to those skilled in the art. Examples of other ingredients include, but are not limited to, tonicity agents, surfactants, antibacterial agents, preservatives, and lubricants (e.g., cellulose derivatives, polyvinyl alcohol, polyvinyl pyrrolidone).

The packaging solution contains a buffering agent in an amount sufficient to maintain the pH of the packaging solution within a desired range, for example, preferably within a physiologically acceptable range of about 6.5 to about 7.5. Any known physiologically compatible buffer can be used. Suitable buffers as an ingredient of a contact lens care composition according to the present invention are known to those skilled in the art. Examples are boric acid, borate (such as sodium borate), citric acid, citrate (such as potassium citrate), bicarbonate (such as sodium bicarbonate), tris (2-amino-2-hydroxymethyl-1, 3-propanediol), bis-tris (bis- (2-hydroxyethyl) -imino-tri- (hydroxymethyl) -methane), bis-amino polyol, triethanolamine, ACES (N- (2 -Hydroxyethyl) -2-aminoethanesulfonic acid), BES (N, N-bis (2-hydroxyethyl) -2-aminoethanesulfonic acid), HEPES (4- (2-hydroxyethyl Yl) -1-piperazine Ethane sulfonic acid), MES (2- (N- (Pinolinyl) ethanesulfonic acid), MOPS (3- [N- (Pinolinyl) -propanesulfonic acid), PIPES (piperazine -N, N'-bis (2-ethanesulfonic acid), TES (N- [tris (hydroxymethyl) methyl] -2-aminoethanesulfonic acid), salts thereof, phosphate buffers (e.g. Na ₂ HPO ₄ , NaH ₂ PO ₄ , and KH ₂ PO ₄ ) or mixtures thereof. Preferably, the buffers are a phosphate buffer, a borate buffer, or a combination thereof. The amount of each buffer in the packaging solution is preferably from 0.001% to 2% by weight, more preferably from 0.01% to 1%, and most preferably from about 0.05% to about 0.30%.

The packaging solution has a tension of from about 200 to about 450 milli-osmotic molecules (mOsm), preferably from about 250 to about 350 mOsm. The tension of the packaging solution can be adjusted by adding organic or inorganic substances that affect the tension. Suitable ocular acceptable tonicity agents include, but are not limited to, sodium chloride, potassium chloride, glycerol, propylene glycol, polyols, mannitol, sorbitol, xylitol, and mixtures thereof.

The packaging solution of the present invention has a viscosity at 25 ° C from about 1 centipoise to about 5 centipoise.

In a preferred embodiment, the packaging solution includes from about 0.01% to about 2%, more preferably from about 0.05% to about 1.5%, and even more preferably from about 0.1% by weight. % To about 1%, and most preferably from about 0.2% to about 0.5% of a water-soluble, heat-crosslinkable, hydrophilic polymer material having a tetrahydroazinonium group.

The packaging solution of the present invention may contain a viscosity enhancing polymer. The viscosity enhancing polymer is preferably non-ionic. Increasing the viscosity of the solution provides a film on the lens that promotes comfortable wearing of the contact lens. The viscosity enhancing component may also function to mitigate the effects on the eye surface during insertion and also to relieve eye irritation.

Preferred viscosity enhancing polymers include, but are not limited to, water-soluble cellulose ethers (e.g., methyl cellulose (MC), ethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose (HEC), hydroxypropyl Cellulose (HPC), hydroxypropyl methylcellulose (HPMC), or mixtures thereof), water-soluble polyvinyl alcohol (PVA), high molecular weight poly (M) having a molecular weight greater than about 2000 (up to 10,000,000 Daltons) Ethylene oxide), polyvinylpyrrolidone, N-vinylpyrrolidone having a molecular weight from about 30,000 to about 1,000,000 Daltons, and at least one (methyl ) Copolymers of dialkylaminoalkyl acrylates, and combinations thereof. Water-soluble cellulose ethers and copolymers of vinylpyrrolidone and dimethylaminoethyl methacrylate are the most preferred viscosity enhancing polymers. Copolymers of N-vinylpyrrolidone and dimethylaminoethylmethacrylate are commercially available, for example, copolymer 845 and copolymer 937 from ISP.

The viscosity enhancing polymer is from about 0.01% to about 5% by weight, preferably from about 0.05% to about 3% by weight, and even more preferably by weight based on the total amount of the packaging solution. An amount of from about 0.1% to about 1% is present in the packaging solution.

The packaging solution may further comprise a polyethylene glycol having a molecular weight of about 1200 or less, more preferably 600 or less, and most preferably from about 100 to about 500 Daltons.

At least one of the cross-linked coating and the packaging solution contains a polymer material having a polyethylene glycol segment, and the packaging solution preferably contains a sufficient amount to have a reduced oxidative degradation of the polyethylene glycol segments. A sensitive amount of alpha- pendant oxygen-polyacid or a salt thereof. Co-owned, co-pending patent application (US Patent Application Publication No. 2004/0116564 A1, which is incorporated herein by reference in its entirety) discloses that pendant-polyacids or their salts can reduce oxidative degradation of polymer materials containing PEG Of sensitivity.

Exemplary alpha-p-oxyl-polyacids or biocompatible salts thereof include, but are not limited to, citric acid, 2-ketoglutarate, or malic acid or biocompatibility (preferably ophthalmic compatibility) salt. More preferably, the α-side oxy-poly acid is citric acid or malic acid or a biocompatible (preferably ophthalmic compatible) salt thereof (for example, sodium, potassium, or the like).

According to the present invention, the packaging solution may further include a mucin-like material, an ophthalmologically beneficial material, and / or a surfactant.

Exemplary mucin-like materials include, but are not limited to, polyglycolic acid, polylactic acid, and the like. Mucin-like materials can be used as guest materials, which can be continuously and slowly released to the ocular surface of the eye for an extended period of time for the treatment of dry eye. Mucin-like materials are preferably present in an effective amount.

Exemplary ophthalmic beneficial materials include, but are not limited to, 2-pyrrolidone-5-carboxylic acid (PCA), amino acids (e.g., taurine, glycine, etc.), alpha hydroxy acids (e.g., glycolic acid, lactic acid , Malic acid, tartaric acid, mandelic acid and citric acid and their salts, etc.), linoleic acid and gamma linoleic acid, and vitamins (for example, B5, A, B6, etc.).

The surfactant can be almost any ocularly acceptable surfactant, including non-ionic, anionic and amphoteric surfactants. Examples of preferred surfactants include, but are not limited to, poloxamer (e.g., Pluronic® F108, F88, F68, F68LF, F127, F87, F77, P85, P75, P104 and P84), polyamines ( For example, Tetronic® 707, 1107, and 1307), polyethylene glycol esters of fatty acids (for example, Tween® 20, Tween® 80), polyoxyethylene or polyoxypropylene ethers of C ₁₂ -C ₁₈ alkanes (for example, Brij® 35), polyoxyethylene stearate (Myrj® 52), polyoxyethylene propylene glycol stearate (Atlas® G 2612), and amphoteric surfactants under the trade names Mirataine® and Miranol®.

It is believed that the viscosity-enhancing polymer, polyethylene glycol, mucin-like material, ophthalmic benefit material, and surfactant present in the packaging solution can be embedded in the polymer matrix of the hydrogel coating And then released into the eyes when worn.

According to a preferred embodiment of the present invention, the elastic modulus (E _CHCA ) of the colored contact lens is about ± 10% or less (preferably about ± 8%, even more preferably about ± 6%). ) Is equal to the elastic modulus (E _PHCA ) of the preformed hydrogel contact lens. The margin (ΔE%) is calculated according to the following equation.

In another aspect, the present invention provides a colored hydrogel contact lens comprising: a hydrogel lens body having an opaque color image thereon and / or therein; and a coating, the A coating encapsulates the hydrogel lens body and the opaque color image, wherein the coating comprises an anchor layer of a polyanionic polymer and a layer of a hydrogel material, wherein the polyanionic polymer is one or more acrylic, methyl Homopolymer or copolymer of methacrylic acid, ethacrylic acid, or 2- (meth) acrylamidoglycolic acid, wherein the hydrogel material is derived from a water-soluble, heat-crosslinkable compound having a tetrahydroazine group And a covalently attached hydrophilic polymer material and are covalently attached to the anchor layer of the polyanionic polymer by a bond each formed between a carboxyl group and a tetrahydroazine group. Colored contact lenses in a hydrated state have about 2 or less after 7 cycles of manual rubbing (preferably about 1.5 or less, more preferably about 1.0 or less, even more preferably about 0.5 or lower).

The hydrogel lens body has a three-dimensional shape of a colored contact lens. According to the present invention, after being subjected to a surface treatment (coater described hereinabove), the prefabricated hydrogel contact lens having a color image thereon and / or therein becomes a hydrogel lens body.

In a preferred embodiment, the hydrogel lens is a non-silicone hydrogel lens body. Preferably, the non-silicone hydrogel lens body is composed of a polymer having at least 50% repeating units of at least one hydroxyl-containing vinyl monomer in terms of moles, and the vinyl monomer is preferred Is selected from the group consisting of: hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, hydroxybutyl (meth) acrylate, glycerol (meth) acrylate, hydroxyethyl (Meth) acrylamide, hydroxypropyl (meth) acrylamide, hydroxybutyl (meth) acrylamide, vinyl alcohol, allyl alcohol, and combinations thereof. More preferably, the polymer further includes at least one repeating unit of a vinylamine-containing vinyl monomer, and the vinyl monomer is preferably selected from the group consisting of (meth) acrylic acid Amine, N, N-dimethyl (meth) acrylamide, N-vinylpyrrolidone (NVP), N-vinylformamide, N-vinylacetamide, N-vinyl isopropylamine N-vinylamine, N-vinyl-N-methylacetamide, N, N-dimethylaminopropyl (meth) acrylamide, N-methyl-3-methylene-2-pyrrole Pyridone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2- Pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, and combinations thereof.

In another preferred embodiment, the hydrogel lens is a polyvinyl alcohol-based hydrogel in contact with the lens body.

In another preferred embodiment, the hydrogel lens is a silicone hydrogel lens body.

Preferably, the hydrogel contact lens body comprises a polymer matrix, a first leachable polymer lubricant and a second leachable polymer lubricant, wherein the first and second leachable polymer lubricants are not Covalently attached to but distributed within the polymer matrix, wherein the second leachable polymer lubricant has at least about 3 times the average molecular weight of the first leachable polymer lubricant Average molecular weight.

According to the present invention, the colored contact lens has a water content (at room temperature, preferably from about 15% to about 80%, more preferably from about 30% to about 70% by weight) when fully hydrated. At about 22 ° C to 28 ° C), and from about 0.2 MPa to about 1.5 MPa (preferably from about 0.3 MPa to about 1.2 MPa, more preferably from about 0.4 MPa to about 1.0 MPa).

In a preferred embodiment, the coating of the colored contact lens of the present invention has at least 0.1 μm (preferably at least 0.5 μm, more preferably at least 1.0 μm, even more preferably from 2.0 μm to about 15 μm).

The average thickness of the coating can be determined from an AFM image of a cross section of the colored hydrogel contact lens of the present invention as is well known to those skilled in the art. Those skilled in the art are very familiar with how to cut contact lenses.

All the various embodiments of the water-soluble, heat-crosslinkable hydrophilic polymer material described above are incorporated in this aspect of the invention.

Although various embodiments of the invention have been described using specific terms, devices, and methods, such descriptions are for illustrative purposes only. The words used are descriptive rather than restrictive. It should be understood that changes and variations can be made by those skilled in the art without departing from the spirit or scope of the invention as set forth in the scope of the following patent applications. In addition, it should be understood that aspects of the various embodiments may be interchanged in whole or in part or may be combined and / or used together in any manner, as explained below:

A method for producing a colored contact lens, the method comprising the following steps: (1) obtaining a prefabricated hydrogel contact lens, the contact lens having a hydrogel lens body and a front surface of the hydrogel lens body and A color image printed with an ink on and / or in one of the rear surfaces, wherein the ink contains pigment particles and optionally one or more dyes; (2) contacting the prefabricated hydrogel with a lens at about 4.0 or less The first coating aqueous solution of the polyanionic polymer at pH and at a coating temperature of from about 25 ° C to about 80 ° C is contacted to obtain a colored contact lens precursor having the color image thereon and the The prefabricated hydrogel contact lens of a layer of a polyanionic polymer, wherein the polyanionic polymer is one or more of acrylic, methacrylic, ethacrylic, 2-propenylaminoglycolic acid, or 2-methacrylic acid A homopolymer or copolymer of aminoglycolic acid, wherein the layer of the polyanionic polymer encapsulates the prefabricated hydrogel contact lens having the color image; and (3) the colored product obtained in step (2) Contact lens precursors include In a second aqueous coating solution of a water-soluble and heat-crosslinkable hydrophilic polymer material having a tetrahydroazinonium group, heating is performed at a temperature of from about 60 ° C to about 140 ° C for at least 30 minutes for crosslinking The water-soluble, heat-crosslinkable hydrophilic polymer material and the polyanionic polymer to form the colored contact lens with a hydrogel coating, the hydrogel coating being covalently attached to the polyanionic polymer Layer, wherein the colored contact lens in a fully hydrated state has a friction level of about 2 or less after 7 cycles of manual rubbing.

2. The method according to invention 1, wherein the first coating aqueous solution has a pH of about 3.5 or less.

3. The method of invention 1, wherein the first coating aqueous solution has a pH of about 3.0 or less.

4. The method of invention 1, wherein the first coating aqueous solution has a pH from about 0.5 to about 2.5.

5. The method according to any one of inventions 1 to 4, wherein the coating temperature is from about 30 ° C to about 75 ° C.

6. The method according to any one of inventions 1 to 4, wherein the coating temperature is from about 35 ° C to about 70 ° C.

7. The method according to any one of inventions 1 to 4, wherein the coating temperature is from about 40 ° C to about 60 ° C.

8. The method according to any one of inventions 1 to 7, wherein the preformed hydrogel contact lens is contacted with the first coating aqueous solution for a contact time of at least one minute.

9. The method according to any one of inventions 1 to 7, wherein the preformed hydrogel contact lens is contacted with the first coating aqueous solution for a contact time of at least 5 minutes.

10. The method according to any one of inventions 1 to 7, wherein the preformed hydrogel contact lens is contacted with the first coating aqueous solution for a contact time of at least 10 minutes.

11. The method according to any one of inventions 1 to 7, wherein the preformed hydrogel contact lens is contacted with the first coating aqueous solution for a contact time of at least 30 minutes.

12. The method according to any one of inventions 1 to 11, wherein the colored material is immersed in the second coating aqueous solution at a temperature of from about 115 ° C to about 125 ° C in a sealed lens package. The contact lens precursor is autoclaved for about 30 minutes to about 90 minutes to perform the heating step, wherein the second coating aqueous solution is a buffered aqueous solution having a pH from 6.7 to 7.6.

13. The method of any one of inventions 1 to 12, wherein the elastic modulus of the colored contact lens is equal to the elastic modulus of the prefabricated hydrogel contact lens within a margin of about ± 10% or less.

14. The method of any one of Inventions 1 to 12, wherein the elastic modulus of the colored contact lens is equal to the elastic modulus of the prefabricated hydrogel contact lens within a margin of about ± 8% or less.

15. The method of any one of Inventions 1 to 12, wherein the elastic modulus of the colored contact lens is equal to the elastic modulus of the prefabricated hydrogel contact lens within a margin of about ± 6% or less.

16. A colored contact lens comprising: a hydrogel lens body having an opaque color image thereon and / or therein; and a coating that encapsulates the hydrogel lens body and the opaque color image, wherein The coating comprises an anchor layer of a polyanionic polymer and a layer of a hydrogel material, wherein the polyanionic polymer is one or more of acrylic acid, methacrylic acid, ethacrylic acid, 2-acrylamidoglycolic acid, or Homopolymer or copolymer of 2-methacrylamidoglycolic acid, wherein the hydrogel material is derived from a water-soluble, heat-crosslinkable, hydrophilic polymer material having a tetrahydroazinonium group and by Each of the bonds formed between a carboxyl group and a tetrahydroaziridinium group is covalently attached to the anchor layer of the polyanionic polymer, wherein the colored contact lens in a fully hydrated state has 7 A friction level of about 2 or less after cyclic manual friction.

17. The colored contact lens according to invention 16 or the method according to any one of inventions 1 to 15, wherein the hydrogel lens is a non-silicone hydrogel lens body.

18. The colored contact lens or method according to invention 17, wherein the non-silicone hydrogel lens body is composed of a first polymer containing at least 50% by mole of repeating units of at least one hydroxyl-containing vinyl monomer composition.

19. The colored contact lens or method of invention 18, wherein the at least one hydroxyl-containing vinyl monomer is selected from the group consisting of: hydroxyethyl (meth) acrylate, 2-hydroxypropyl (Meth) acrylate, 3-hydroxypropyl (meth) acrylate, glycerol (meth) acrylate, N-2-hydroxyethyl (meth) acrylamide, N-2-hydroxypropyl ( (Meth) acrylamide, N-3-hydroxypropyl (meth) acrylamide, N, N-bis (hydroxyethyl) (meth) acrylamide, N-2,3-dihydroxypropyl (Meth) acrylamide, N -tris (hydroxymethyl) methyl (meth) acrylamide, vinyl alcohol, allyl alcohol, and combinations thereof.

20. The colored contact lens or method according to invention 19, wherein the first polymer further comprises repeating units of at least one vinyl monomer containing vinylamine.

21. The colored contact lens or method of invention 20, wherein said at least one vinylamine-containing vinyl monomer is selected from the group consisting of (meth) acrylamidonium, N, N-di Methyl (meth) acrylamide, N-vinylpyrrolidone (NVP), N-vinylformamide, N-vinylacetamide, N-vinylisopropylamidine, N-ethylene -N-methylacetamide, N, N-dimethylaminopropyl (meth) acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl -3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl Methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, and combinations thereof.

22. The colored contact lens or method according to invention 17, wherein the non-silicone hydrogel lens body is composed of a crosslinked product of a water-soluble, actinically crosslinkable polyvinyl alcohol prepolymer.

23. The colored contact lens or method of invention 22, wherein the water-soluble, actinically crosslinkable polyvinyl alcohol prepolymer comprises: at least 60% repeat units of vinyl alcohol (ie, ); From about 1% to about 25% of repeat units with formula (I) in moles; and

Among them: R ₃ is hydrogen or C ₁ -C ₆ alkyl; R ₄ is C ₁ -C ₆ alkylene divalent; R ₅ is hydrogen or C ₁ -C ₆ alkyl; R ₆ is or Ethylenically unsaturated groups, wherein q1 and q2 are independently zero or 1 and R ₇ and R ₈ are independently C ₂ -C ₈ alkylene divalent groups, and R ₉ is C ₂ -C ₈ Alkenyl.

24. The colored contact lens or method according to invention 23, wherein in formula (I), R ₃ is hydrogen.

25. The colored contact lens or method according to invention 23 or 24, wherein in formula (I), R ₄ is a C ₁ -C ₄ alkylidene divalent group.

26. The colored contact lens or method according to the invention 23 or 24, wherein in the formula (I), R ₄ is a methylene or butylene divalent group.

27. The colored contact lens or method according to invention 23 or 24, wherein in formula (I), R ₄ is a methylene divalent group.

28. The colored contact lens or method according to any one of Inventions 23 to 27, wherein in formula (I), R ₅ is hydrogen or a C ₁ -C ₄ alkyl group.

29. The colored contact lens or method according to any one of Inventions 23 to 27, wherein in the formula (I), R ₅ is hydrogen or methyl or ethyl.

30. The colored contact lens or method according to any one of Inventions 23 to 27, wherein in formula (I), R ₅ is hydrogen or methyl.

31. The colored contact lens or method according to any one of Inventions 23 to 30, wherein in the formula (I), R ₄ is a methylene divalent group, R ₅ is a hydrogen group or a C ₁ -C ₄ alkyl group , R ₃ is hydrogen, and R ₆ is Group, wherein R ₉ q2 zero-based vinyl-based (* -CH = CH ₂₎ or 1-methyl-vinyl _{(* -C (CH 3) =} CH 2).

32. The colored contact lens or method of any one of Inventions 23 to 31, wherein the polyvinyl alcohol prepolymer has a weight average molecular weight of at least 2,000 Daltons and comprises from about 2% to About 15% have repeating units of formula (I).

33. The colored contact lens according to the invention 16 or the method according to any one of the inventions 1 to 15, wherein the hydrogel lens is a system silicone hydrogel lens body.

34. The colored contact lens according to any one of inventions 16 to 33 or the method according to any one of inventions 1-15 and 17-33, wherein the hydrogel lens body comprises a polymer matrix and one or A variety of leachable polymer lubricants, wherein the leachable polymer lubricants are not covalently attached to the polymer matrix but are distributed within the polymer matrix.

35. The colored contact lens or method of invention 34, wherein the leachable polymer lubricant is a non-crosslinkable hydrophilic polymer selected from the group consisting of: polyvinyl alcohol ( PVA); polyamides; polyimines; polylactones; homopolymers of N-vinylpyrrolidone; copolymers of N-vinylpyrrolidone and one or more hydrophilic vinyl comonomers; A homopolymer of (meth) acrylamide; a copolymer of (meth) acrylamide with one or more hydrophilic vinyl monomers; a homopolymer of N-vinyl-N-methylacetamide; Copolymers of N-vinyl-N-methylacetamide with one or more hydrophilic vinyl monomers; homopolymers of C ₂ -C ₃ hydroxyalkyl (meth) acrylamide; C ₂ -C Copolymers of ₃ hydroxyalkyl (meth) acrylamide and one or more hydrophilic vinyl monomers; copolymers of a vinyl monomer containing phosphinocholine and one or more hydrophilic vinyl monomers; poly (Ethylene oxide) (PEO); poly (2-ethyl Oxazoline); heparin polysaccharides; polysaccharides; and mixtures thereof.

36. The colored contact lens according to any one of inventions 16-35 or the method according to any one of inventions 1-15 and 17-35, wherein the colored contact lens in a fully hydrated state has between seven A friction level of about 1.5 or less after cyclic manual friction.

37. The colored contact lens according to any one of inventions 16-35 or the method according to any one of inventions 1-15 and 17-35, wherein the colored contact lens in a fully hydrated state has between seven A friction level of about 1.0 or less after cyclic manual friction.

38. The colored contact lens according to any one of inventions 16-35 or the method according to any one of inventions 1-15 and 17-35, wherein the colored contact lens in a fully hydrated state has between seven A friction level of about 0.5 or less after cyclic manual friction.

39. The colored contact lens according to any one of inventions 16-38 or the method according to any one of inventions 1-15 and 17-38, wherein the colored contact lens has a weight basis when fully hydrated Water content from about 15% to about 80% (at room temperature, at about 22 ° C to 28 ° C).

40. The colored contact lens according to any one of inventions 16-38 or the method according to any one of inventions 1-15 and 17-38, wherein the colored contact lens has a weight basis when fully hydrated Water content from about 30% to about 70% (at room temperature, at about 22 ° C to 28 ° C).

41. The colored contact lens according to any one of inventions 16-40 or the method according to any one of inventions 1-15 and 17-40, wherein the colored contact lens has from about 0.2 when fully hydrated Modulus of elasticity from MPa to about 1.5 MPa.

42. The colored contact lens according to any one of inventions 16-40 or the method according to any one of inventions 1-15 and 17-40, wherein the colored contact lens has a range from about 0.3 when fully hydrated Modulus of elasticity from MPa to about 1.2 MPa.

43. The colored contact lens according to any one of inventions 16-40 or the method according to any one of inventions 1-15 and 17-40, wherein the colored contact lens has a thickness from about 0.4 when fully hydrated Modulus of elasticity from MPa to about 1.0 MPa.

44. The colored contact lens according to any one of inventions 16-43 or the method according to any one of inventions 1-15 and 17-43, wherein the coating has a thickness of at least 0.1 μm.

45. The colored contact lens according to any one of inventions 16-43 or the method according to any one of inventions 1-15 and 17-43, wherein the coating has a thickness of at least 0.5 μm.

46. The colored contact lens according to any one of inventions 16-43 or the method according to any one of inventions 1-15 and 17-43, wherein the coating has a thickness from about 1.0 μm to about 15 μm .

47. The colored contact lens according to any one of inventions 16-46 or the method according to any one of inventions 1-15 and 17-46, wherein the polyanionic polymer is poly (acrylic acid) (PAA) , Poly (methacrylic acid) (PMAA), poly (acrylic acid-co-methacrylic acid) (pAA-pMAA), poly (ethyl acrylic acid) (PEAA), poly (acrylic acid-co-ethyl acrylic acid) (pAA- pEAA), poly (methacrylic acid-co-ethyl acrylic acid) (pMAA-pEAA), poly [2-acrylic acid aminoglycolic acid], poly [2-methacrylic acid aminoglycolic acid], or a combination thereof .

48. The colored contact lens according to any one of inventions 16-46 or the method according to any one of inventions 1-15 and 17-46, wherein the polyanionic polymer is poly (acrylic acid) (PAA) , Poly (methacrylic acid) (PMAA), poly (acrylic acid-co-methacrylic acid) (pAA-pMAA), or a combination thereof.

49. The colored contact lens or method of invention 47 or 48, wherein the polyanionic polymer has a weight average molecular weight of at least 100,000 Daltons.

50. The colored contact lens or method of invention 47 or 48, wherein the polyanionic polymer has a weight average molecular weight from 200,000 to 10,000,000 Daltons.

51. The colored contact lens or method according to invention 47 or 48, wherein the polyanionic polymer has a weight average molecular weight from 300,000 to 5,000,000 Daltons.

52. The colored contact lens or method according to invention 47 or 48, wherein the polyanionic polymer has a weight average molecular weight from 400,000 to 3,000,000 Daltons.

53. The colored contact lens according to any one of inventions 16-52 or the method according to any one of inventions 1-15 and 17-52, wherein the water-soluble heat-crosslinkable polymer material comprises ( i) from about 20% to about 95% by weight derived from polyamidoamine-epichlorohydrin or poly (2- The first polymer chain of oxazoline-co-ethyleneimine) -epichlorohydrin, (ii) a hydrophilic moiety from about 5% to about 80% by weight, each derived from at least one having at least one reactive functional group The first hydrophilicity enhancer, the reactive functional group is selected from the group consisting of a primary amine group, a secondary amine group, a carboxyl group, a thiol group, and a combination thereof (preferably a carboxyl group), wherein The hydrophilic moieties are supported by one or more of a tetrahydroazinonium group of the polyamidoamine-epichlorohydrin and an amine, carboxyl, or thiol group of the first hydrophilicity enhancer. Covalent bonds formed between them are covalently attached to the first polymer chains, and (iii) a tetrahydroazinonium group, which are part of the first polymer chains or Is a pendant or end group covalently attached to the first polymer chain.

54. The colored contact lens according to any one of inventions 16-52 or the method according to any one of inventions 1-15 and 17-52, wherein the water-soluble heat-crosslinkable polymer material comprises ( i) from about 20% to about 95% by weight derived from polyamidoamine-epichlorohydrin or poly (2- The first polymer chain of oxazoline-co-ethyleneimine) -epichlorohydrin, (ii) from about 5% to about 80% by weight of the second polymer chain, each derived from at least one having at least one reaction A second hydrophilicity enhancer of a functional group, the reactive functional group is selected from the group consisting of a primary amine group, a secondary amine group, a carboxyl group, a thiol group, and a combination thereof (preferably a carboxyl group) Wherein the second polymer chains are supported by one or more tetrahydroazine groups each in the polyamidoamine-epichlorohydrin and an amine group, carboxyl group or Covalent bonds formed between thiol groups and covalently attached to the first polymer chains, and (iii) a tetrahydroazinonium group, the groups being the first polymer Part of the chain is either a pendant or end group that is covalently attached to the first polymer chain.

55. The colored contact lens or method according to invention 53, wherein the first hydrophilicity enhancer is a monosaccharide containing a primary amine, a monosaccharide containing a secondary amine, a monosaccharide containing a carboxyl group, and a monosaccharide containing a thiol , Disaccharides containing primary amines, disaccharides containing secondary amines, disaccharides containing carboxyl groups, disaccharides containing thiols, oligosaccharides containing primary amines, oligosaccharides containing secondary amines, oligosaccharides containing carboxyl groups, A thiol-containing oligosaccharide, or a combination thereof.

56. The colored contact lens or method according to invention 54, wherein the second hydrophilicity enhancer is: polyethylene glycol having a unique amine group, carboxyl group or thiol group; having two terminal amine groups, Polyethylene glycols having carboxyl and / or thiol groups; multi-arm polyethylene glycols having one or more amine, carboxyl, and / or thiol groups; having one or more amine, carboxyl, and / or Polyethylene glycol dendrimers with thiol groups.

57. The colored contact lens or method according to invention 54, wherein the second hydrophilicity-enhancing copolymer is a polymerization product of a composition comprising (1) about 60% by weight Or less one or more reactive vinyl monomers and (2) one or more non-reactive hydrophilic vinyl monomers.

58. The colored contact lens or method of invention 57 wherein said one or more reactive vinyl monomer systems have a vinyl monomer having a carboxyl group.

59. The invention group or colored contact lenses The method of claim 58, wherein the one or more reactive vinyl monomer is selected from the group consisting of: acrylic acid, C ₁ -C ₄ alkyl acrylate (e.g., methyl Acrylic acid, ethacrylic acid, propyl acrylic acid, butyl acrylic acid), N-2-acrylic acid aminoglycolic acid, β-methacrylic acid (crotonic acid), α-phenylacrylic acid, β-acrylic acid Acid, sorbic acid, behenic acid, cinnamic acid, 1-carboxy-4-phenylbutadiene-1,3, itaconic acid, citraconic acid, mesaconic acid, pentenedioic acid, aconic acid, maleic acid , Fumaric acid, tricarboxyethylene, and combinations thereof.

60. The colored contact lens or method of invention 58, wherein the one or more reactive vinyl monosystem acrylic, methacrylic, or a combination thereof.

61. The colored contact lens or method of invention 57 wherein said one or more reactive vinyl monomer systems have a primary or secondary amine-based vinyl monomer.

62. The colored contact lens or method of invention 61, wherein the one or more reactive vinyl monosystem amine-C ₂ -C ₆ alkyl (meth) acrylate, C ₁ -C ₆ alkane Aminoamino-C ₂ -C ₆ alkyl (meth) acrylate, allylamine, vinylamine, amino-C ₂ -C ₆ alkyl (meth) acrylamidonium, C ₁ -C ₆ Alkylamino-C ₂ -C ₆ alkyl (meth) acrylamidonium, or a combination thereof.

63. The colored contact lens or method of any one of Inventions 57 to 62, wherein the one or more non-reactive vinyl monomers are selected from the group consisting of (meth) acrylamide , N, N-dimethyl (meth) acrylamide, N-vinylpyrrolidone (NVP), N-vinylformamide, N-vinylacetamide, N-vinylisopropyl Amidine, N-vinyl-N-methylacetamide, N, N-dimethylaminoethyl (meth) acrylate, N, N-dimethylaminopropyl (meth) acrylic acid Amine, glycerol (meth) acrylate, N-2-hydroxyethyl (meth) acrylamide, N-2-hydroxypropyl (meth) acrylamide, N-3-hydroxypropyl (methyl) Acrylamide, N, N-bis (hydroxyethyl) (meth) acrylamide, N-2,3-dihydroxypropyl (meth) acrylamide, N -tris (hydroxymethyl) methyl (Meth) acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5- Methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3 -Methylene-2-pyrrolidone, 2-hydroxyethyl (meth) acrylate, hydroxy (meth) acrylate Esters, having up to 1500 Daltons weight average molecular weight of C ₁ -C ₄ - alkoxy polyethylene glycol (meth) acrylate, allyl alcohol, vinyl alcohol, and combinations thereof.

64. The colored contact lens or method of any one of Inventions 57 to 62, wherein the one or more non-reactive vinyl monomers are selected from the group consisting of acrylamide, N, N -Dimethacrylamide, N-vinylpyrrolidone, Phosphocholine-containing vinyl monomer, N-vinyl-N-methylacetamide, glycerol (meth) acrylate, (formaldehyde) yl) acrylate, N- hydroxyethyl (meth) acrylamide, up to 400 Daltons having a weight average molecular weight of C ₁ -C ₄ - alkoxy polyethylene glycol (meth) acrylate , Vinyl alcohol, and combinations thereof.

65. The colored contact lens or method of any one of Inventions 57 to 62, wherein the one or more non-reactive vinyl monosystems contain a vinyl monomer of phosphatidylcholine.

66. The colored contact lens or method of any one of Inventions 57 to 62, wherein the one or more non-reactive vinyl monosystem methacryloxyethylphosphonium choline.

67. The colored contact lens or method of any one of Inventions 57 to 66, wherein the composition comprises about 50% or less of the one or more reactive vinyl monomers.

68. The colored contact lens or method of any one of Inventions 57 to 66, wherein the composition comprises from about 0.1% to about 30% by weight of the one or more reactive vinyl monomers.

69. The colored contact lens or method of any one of Inventions 57 to 66, wherein the composition comprises from about 0.5% to about 20% by weight of the one or more reactive vinyl monomers.

70. The colored contact lens or method of any one of Inventions 57 to 66, wherein the composition comprises from about 1% to about 15% by weight of the one or more reactive vinyl monomers.

71. The colored contact lens or method according to invention 54, wherein the second hydrophilicity enhancer is a polysaccharide containing a primary amine, a polysaccharide containing a secondary amine, a polysaccharide containing a carboxyl group, hyaluronic acid, chondroitin sulfate, or Its combination.

The above disclosure should enable those skilled in the art to practice the invention. Various modifications, changes, and combinations can be made to the various embodiments described herein. In order to enable the reader to better understand its specific implementation and advantages, it is recommended to refer to the following examples. It is intended that the specification and examples be considered exemplary.

Example 1

Manual friction test.

The lenses were manually rubbed with a RENU® multifunctional lens care solution (or another multifunctional lens care solution or phosphate buffered saline) for 20 seconds according to the product instruction manual and returned to the lens cover containing fresh lens care solution. The above procedure is repeated a given number of times, for example from 1 to 30 times (ie the number of iterations of a manual friction test simulating a cleaning and soaking cycle). As used in this application, the term "i-cycle manual friction" (e.g., 7-cycle manual friction) means i (e.g., 7) iterations described above for simulating cleaning and soaking cycles Manual friction test.

Evaluation of lubricity.

The lubricity of the lenses was evaluated by using a finger-feeling lubricity test, which qualitatively characterizes the smoothness of the lens surface on a scale of friction from 0 to 4. The higher the friction level, the lower the slip (or lubricity).

Commercial lenses: DAILIES® TOTAL1®; ACUVUE® OASYS ^TM ; ACUVUE® ADVANCE PLUS ^TM ; DAILIES® Aqua Comfort Plus®; and AIR OPTIX® have been assigned friction levels (indicated as “FR” below) of 0, 1, 2, 3, and 4. They were used as standard lenses to determine the level of friction of the lenses under test.

The samples were placed in PBS for at least two 30-minute rinses each, and then transferred to fresh PBS for evaluation afterwards. Prior to evaluation, hands were rinsed with soap, extensively with deionized water and then dried with a KimWipe® towel. The samples are processed between fingers and a value is assigned to each sample relative to the above standard lenses. For example, if the lenses are determined to be only slightly better than the AIR OPTIX ^™ lenses, they are assigned the number 3. The value of the friction rating is averaged by the results of at least two friction ratings of the contact lens by two or more individuals and / or by two or more contact lenses (from the same batch by one person) Lens production) The value obtained by averaging the friction levels.

The finger's lubricity (ie, friction level) of a contact lens can be determined according to the procedure described above: direct lack of out-of-pack (so-called "OOP lubricity" or "OOP friction level") but at 30 min immersion in PBS) or after manual rubbing for i cycles (eg, 7 cycles) (so-called "AiCMR lubricity" or "AiCMR friction grade").

Surface wettability test.

The water contact angle (WCA) on a contact lens is a general measure of the surface wettability of a contact lens. In particular, a low water contact angle corresponds to a more wettable surface. A VCA 2500 XE contact angle measuring device (from AST Corporation in Boston, Massachusetts) was used to measure the average contact angle of the contact lenses (lying drop method). This device is capable of measuring forward contact angle (θ _a ) or backward contact angle (θ _r ) or fixed (static) contact angle. Unless specified, water contact angles are fixed (static) contact angles. These measurements were performed on fully hydrated contact lenses and immediately after blotting as follows. The contact lens was removed from the vial and washed 3 times in approximately 200 ml of fresh deionized water to remove loosely bound packaging additives from the lens surface. The lens was then placed on top of a lint-free cleaning cloth (Alpha Wipe TX1009), wiped lightly to remove surface water, mounted on the contact angle measurement stand, blow dried with a stream of dry air, and finally used by The software provided by the manufacturer automatically measures the contact angle of the drop. The deionized water used to measure the contact angle has a resistivity of> 18 MΩcm and the droplet volume used is 2 μl. Typically, uncoated silicone hydrogel lenses (after autoclaving) have a lying drop contact angle of about 120 degrees. Before starting contact with the contact lens, the tweezers and holder were thoroughly washed with isopropyl alcohol and rinsed with deionized water.

Water Burst Time (WBUT) test.

The surface hydrophilicity of the lenses (after autoclaving) is determined by S. Bhamla, in Langmuir [31, 3820-3828, 2015] and by S. Bhamla and coworkers, in Investigative Ophthalmology & Visual Science [In the study of Ophthalmology and Vision Science], 57,949-958, 2016 (by incorporating by reference in its entirety herein) the technique described (iDDrOP) to determine the water break time and break rate on the surface of the contact lens. To begin the process, the lens is placed on an immersed mount. After forcing the lens through the PBS-air interface, a pendant camera (with special lighting and filters) records the time (water break time, or WBUT) when the liquid interface begins to break on the lens. In addition, it is possible to measure how well the surface continues to hold the liquid after rupture (for example, a total liquid coverage from 90% to 80% equal to the ratio of wet area over the total area). A plot of total liquid coverage versus time can be used to calculate the rupture rate by determining the slope of the line.

TBO uptake test

Toluidine blue O (TBO) is a positively charged dye that has been frequently used to quantify the concentration of negatively charged polymers. See, for example, Hutter, J., J. Soc. Cosmet. Chem. [Cosmetic Chemistry Association], 42, 87-96 , 1991; Roediger, S., Anal. Chem. [Analytical Chemistry] , 83 , 3379- 3385, 2011; and Tiraferri, A., Elimelech, M, J. Mem Sci [Journal of Medical Science], 389 , 499-508, 2012 (herein incorporated by reference in its entirety).

To estimate the amount of negatively charged groups on the surface of the lens, the lens was placed in 10 ppm toluidine blue (2 ml / well in a 24-well dish) in a phosphate buffer solution and cultured overnight. After removing these lenses, the remaining TBO can be monitored by measuring the absorbance of the dye at 630 nm to estimate the TBO uptake of each lens. The TBO uptake of each lens is proportional to the concentration of negatively charged groups on the surface of the lens.

TBO stain test

It is known that as the dye tightly becomes stacked together in a strongly negatively charged polymer matrix, the color of the dye can change (from blue to red) when the dye tightly becomes stacked together with a strong change. ) (Jebaramya, J., digest J.Nano.Biostructures [ magazine nano structure of biological digestion], 4, 789-797,2009, incorporated in its entirety by reference herein). This allows the presence and uniformity of the coating to be observed.

The lenses were placed in 10 ppm toluidine blue (2 ml / well in a 24-well petri dish) in a phosphate buffer solution and cultured overnight. These lenses were then removed from the hole and checked for color changes. If the color of the dye changes from blue to purple or red (ie, red shift or metachromism), a densely packed acidic IPC / anchor layer is formed on the lens surface. It should be understood that the lenses involved in the TBO uptake test can be used in this test.

In addition, by observing the enlarged image, the print quality or color can be checked.

Example 2

Preparation of PAA aqueous solution. Polyacrylic acid (PAA) was prepared by adding a sufficient amount of PAA (Carpobol 907, Mw ~ 450K Daltons) to water (distilled or deionized water) to have a concentration of about 0.1% by weight. Water solution. After the PAA was completely dissolved, the pH was adjusted to about 2 by adding ~ 1.87% of formic acid to the aqueous PAA solution. The prepared PAA aqueous solution was filtered to remove any particles or foreign matter.

Phosphate buffered saline (PBS) is prepared by the following methods: NaH ₂ PO ₄ . H ₂ O, Na ₂ HPO ₄ . 2H ₂ O is dissolved in a given volume of purified water (distilled or deionized) to have the following composition: approximately 0.044 w / w% NaH ₂ PO ₄ . H ₂ O, about 0.388 w / w /% Na ₂ HPO ₄ . 2H ₂ O, and approximately 0.79 w / w% NaCl.

Using the same procedure for preparing PBS but without adding NaCl, phosphate buffered saline (PB) (PB, without NaCl) without NaCl can also be prepared.

IPC brine: poly (AAm-co-AA) (90/10) part of sodium salt (about 90% solids content, poly (AAm-co-AA) 90/10, Mw 200,000) was obtained from Polyses Corporation ( Polysciences, Inc.) and used as received. Polyamidamine-epichlorohydrin (PAE) (Kymene, an aqueous solution of different solids content) was purchased from Ashland and used as received. IPC saline was prepared by dissolving about 0.132% w / w poly (AAm-co-AA) (90/10) and about 0.11% w / w PAE in PBS (about 0.044 w / w% NaH ₂ PO ₄ . H ₂ O, about 0.388 w / w /% Na ₂ HPO _{4. 2} H ₂ O, about 0.79 w / w% NaCl) and adjusting the pH to 7.2-7.4. The prepared IPC brine was pretreated at about 65 ° C for about 6 hours. After the thermal pretreatment, the IPC brine was cooled back to room temperature. Up to 5 ppm hydrogen peroxide can be added to the final IPC brine to prevent bioburden growth, and the IPC brine is filtered using a 0.22 micron membrane filter.

Example 3

FreshLook® ONE-DAY (FL1) contact lenses (each of which contains an opaque tint image) are from Alcon® and are used in the examples. The FL1 lens was removed from the package and rinsed with purified water (distilled or deionized water) and immersed in the PAA solution prepared in Example 2 at room temperature for 5 minutes, followed by rinsing in purified water for 2 minutes. PAA-coated FL1 lenses were then placed in a polypropylene blister (i.e., lens packaging housing) with 0.6 mL of the IPC saline (one lens per housing) (half of the saline was added before inserting the lens). The blister was then sealed with foil and autoclaved at about 121 ° C for about 45 minutes to form a transparent hydrogel coating on the FL1 lens. Each transparent hydrogel coating encapsulates the FL1 lens body and the opaque color image.

Example 4

Concentration of negatively charged groups

The concentration of negatively charged groups on the lens prepared in Example 3 was determined according to the TBO uptake test described in Example 1. As a control, FL1 lenses were tested in parallel (without a transparent hydrogel coating thereon).

The TBO solution was exposed to a control lens, and the absorbance at 630 nm was found to be about 87% of the absorbance at 630 nm for the original TBO solution (10 ppm TBO). Based on this result, it is estimated that 2.6 g of TBO was incorporated into each control lens. This is thought to be due to the non-specific interaction of TBO with the lens body.

However, when the TBO solution was exposed to a test lens (the one prepared in Example 3), the absorbance at 630 nm was found to be about 45% of the absorbance at 630 nm for the original TBO solution (10 ppm TBO). Based on this result, it is estimated that 11 g of TBO is bound to each test lens, indicating the presence of a relatively large number of negatively charged groups on the surface of the lens (i.e., the PAA base coating and the IPC top coating presence).

By examining the magnified image (10x) of the test lens, it was observed that print quality or color did not appear to be affected by the process of applying a transparent hydrogel coating.

Water break time and rate

Figure 1 shows the results for a control lens (FreshLook® ONE-DAY) and a FreshLook® ONE-DAY lens (i.e., a test contact lens prepared in Example 3) modified to have a transparent hydrogel coating thereon. Total liquid coverage as a function of time. Vividly, this example shows that the control lens has a shorter WBUT than the test lens, and the water break rate (slope of the line) is more gradual for the test lens. Compared to the almost transient rupture of the control lens, the test lens retained much longer water.

A statistical analysis of the iDDrOP results is shown in Table 1. After measuring 3 spots for 3 lenses, the test lens has a WBUT that is more than 5 times larger than the control lens. In addition, the time that the test lenses retain water (from 90% -80% liquid coverage) after the initial break has been improved by almost 90 times.

N = 3 lenses with 3 spots each.

Water retention time is measured between 90% and 80% of total liquid coverage.

Lack of packaging lubricity

OOP lubricity (i.e., FreshLook® ONE-DAY) of a control lens (FreshLook® ONE-DAY) and a FreshLook® ONE-DAY lens (ie, the test contact lens prepared in Example 3) modified to have a transparent hydrogel coating thereon OOP friction rating) was evaluated according to the procedure described in Example 1. It was found that the control lens had an OOP friction rating of 3 and the test lens had an OOP friction rating of 0.

Claims (22)

    A method for producing a soft contact lens, the method includes the following steps: (1) obtaining a prefabricated hydrogel contact lens, the contact lens having a hydrogel lens body and a front surface and a rear surface of the hydrogel lens body A color image printed with and / or on one of the inks, wherein the ink contains pigment particles; (2) contacting the preformed hydrogel with a lens at a pH of about 4.0 or less and at a temperature of from about 25 ° C to A first coating aqueous solution of a polyanionic polymer at a coating temperature of about 80 ° C is contacted to obtain a colored contact lens precursor, the precursor being in contact with the prefabricated hydrogel having a layer of the polyanionic polymer thereon. Lenses, wherein the polyanionic polymer is one or more homopolymers or copolymers of acrylic acid, methacrylic acid, ethacrylic acid, 2-acrylamidoglycolic acid, or 2-methacrylamidoglycolic acid, Wherein the layer of the polyanionic polymer encapsulates the prefabricated hydrogel contact lens having the color image; and (3) the colored contact lens precursor obtained in step (2) is contained in a layer containing a tetrahydroazine group Water-soluble and hot-swappable In the second coating aqueous solution of the hydrophilic polymer material, heated at a temperature from about 60 ° C to about 140 ° C for at least 30 minutes to cross-link the water-soluble heat-crosslinkable hydrophilic polymer material and the poly An anionic polymer to form the colored contact lens, wherein the colored contact lens has a hydrogel coating covalently attached to a layer of the polyanionic polymer, wherein the colored contact lens in a fully hydrated state has A friction level of about 2 or less after each cycle of manual friction.         The method according to item 1 of the patent application scope, wherein the hydrogel lens is a non-silicone hydrogel lens body.         The method according to item 2 of the scope of patent application, wherein the non-silicone hydrogel lens body is composed of a polymer containing at least 50% by mole of repeating units of at least one hydroxyl-containing vinyl monomer.     The method of claim 3, wherein the at least one hydroxyl-containing vinyl monomer is selected from the group consisting of: hydroxyethyl (meth) acrylate, 2-hydroxypropyl (methyl Base) acrylate, 3-hydroxypropyl (meth) acrylate, glycerol (meth) acrylate, N-2-hydroxyethyl (meth) acrylamide, N-2-hydroxypropyl (methyl Acrylamide, N-3-hydroxypropyl (meth) acrylamide, N, N-bis (hydroxyethyl) (meth) acrylamide, N-2,3-dihydroxypropyl (methyl Group) acrylamide, N -tris (hydroxymethyl) methyl (meth) acrylamide, vinyl alcohol, allyl alcohol, and combinations thereof. The method according to item 2 of the scope of patent application, wherein the non-silicone hydrogel lens is obtained by polymerizing an aqueous lens forming composition containing a water-soluble, actinically crosslinkable polyvinyl alcohol prepolymer, The prepolymer comprises: at least 60% repeat units of vinyl alcohol in moles; from about 1% to about 25% repeat units of formula (I) in moles; and Wherein: R ₃ may be hydrogen or C ₁ -C ₆ alkyl; R ₄ is C ₁ -C ₆ alkylene divalent; R ₅ is hydrogen or C ₁ -C ₆ alkyl; R ₆ is or Ethylenically unsaturated groups, wherein q1 and q2 are independently zero or 1 and R ₇ and R ₈ are independently C ₂ -C ₈ alkylene divalent groups, and R ₉ is C ₂ -C ₈ Alkenyl.     The method of claim 1, wherein the prefabricated hydrogel contact lens is a silicone hydrogel lens body.         The method according to any one of claims 1 to 6, wherein the prefabricated hydrogel contact lens is contacted with the first coating aqueous solution for a contact time of at least one minute.         The method according to item 7 of the scope of patent application, wherein the polyanionic polymer is poly (acrylic acid) (PAA), poly (methacrylic acid) (PMAA), poly (acrylic acid-co-methacrylic acid) (pAA- pMAA), poly (ethylacrylic acid) (PEAA), poly (acrylic acid-co-ethylacrylic acid) (pAA-pEAA), poly (methacrylic acid-co-ethylacrylic acid) (pMAA-pEAA), poly [2 -Acrylamidoglycolic acid], poly [2-methacrylamidoglycolic acid], or a combination thereof, wherein the polyanionic polymer has a weight average molecular weight of at least 100,000 Daltons.     The method of claim 8 in which the water-soluble heat-crosslinkable polymer material comprises (i) from about 20% to about 95% by weight derived from polyamidoamine-epichlorohydrin Or poly (2- A first polymer chain of oxazoline-co-ethyleneimine) -epichlorohydrin, (ii) from about 5% to about 80% by weight of a hydrophilic moiety and / or a second polymer chain, wherein The hydrophilic portions are each derived from at least one first hydrophilicity enhancer, which is a monosaccharide containing a primary amine, a monosaccharide containing a secondary amine, a monosaccharide containing a carboxyl group, and a monosaccharide containing a thiol , Disaccharides containing primary amines, disaccharides containing secondary amines, disaccharides containing carboxyl groups, disaccharides containing thiols, oligosaccharides containing primary amines, oligosaccharides containing secondary amines, oligosaccharides containing carboxyl groups, A thiol-containing oligosaccharide, or a combination thereof, wherein the hydrophilic moieties are each supported by a tetrahydroacridium group on the polyamidoamine-epichlorohydrin and an amine of the first hydrophilicity enhancer Covalently attached to the first polymer chains by one or more covalent bonds formed between the amine, carboxyl, or thiol groups, wherein the second polymer chains are each derived from at least one Hydrophilicity enhancer of reactive functional group, the reactive functional group is selected from the group consisting of A primary amine group, a secondary amine group, a carboxyl group, a thiol group, and combinations thereof, wherein the second polymer chains are supported by one or more tetrahydroazines each in the polyamidoamine-epichlorohydrin A covalent bond formed between the sulfonium group and an amine, carboxyl, or thiol group of the second hydrophilic enhancer to be covalently attached to the first polymer chains, and (iii) Tetrahydroazinonium groups, which are part of the first polymer chains or are pendant or end groups covalently attached to the first polymer chains. The method of claim 9 in which the water-soluble heat-crosslinkable polymer material comprises the second polymer chain from about 5% to about 80% by weight, wherein the second hydrophilic Sex enhancer system: polyethylene glycol with one unique amine, carboxyl or thiol group; polyethylene glycol with two terminal amine, carboxyl and / or thiol groups; one or more Multi-arm polyethylene glycols with amine, carboxyl, and / or thiol groups; polyethylene glycol dendrimers with one or more amine, carboxyl, and / or thiol groups; polysaccharides containing primary amines Polysaccharides containing secondary amines; polysaccharides containing carboxyl groups; hyaluronic acid; chondroitin sulfate; copolymers, the copolymers are polymerized products of a composition comprising (1) about 60% or more by weight Less one or more reactive vinyl monomers and (2) one or more non-reactive hydrophilic vinyl monomers, wherein the one or more reactive vinyl monomer systems have a carboxyl group, a primary amine group, or two Grade amine-based vinyl monomer, wherein the one or more non-reactive vinyl monomers A group consisting of: vinyl monomers containing phosphatidylcholine, (meth) acrylamide, N, N-dimethyl (meth) acrylamide, N-vinylpyrrolidone (NVP), N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, (meth) acrylic acid N, N-dimethylaminoethyl, N, N-dimethylaminopropyl (meth) acrylamide, glycerol (meth) acrylate, N-2-hydroxyethyl (meth) acrylamine Amine, N-2-hydroxypropyl (meth) acrylamide, N-3-hydroxypropyl (meth) acrylamide, N, N-bis (hydroxyethyl) (meth) acrylamide, N-2,3-Dihydroxypropyl (meth) acrylamide, N -tris (hydroxymethyl) methyl (meth) acrylamide, N-methyl-3-methylene-2-pyrrole Pyridone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2- Pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth) acrylate, ( meth) acrylate having up to 1500 Daltons weight average molecular weight of C ₁ -C ₄ - alkoxy polyethylene Alcohol (meth) acrylate, allyl alcohol, vinyl alcohol, and combinations thereof; or combinations thereof.     The method of claim 10, wherein the colored contact lens precursor is immersed in the second coating aqueous solution at a temperature of from about 115 ° C to about 125 ° C in a sealed lens package. The heating step is performed by autoclaving for about 30 minutes to about 90 minutes, wherein the second coating aqueous solution is a buffered aqueous solution having a pH from 6.7 to 7.6.         A colored contact lens comprising: a hydrogel lens body having an opaque color image thereon and / or therein; and a coating that encapsulates the hydrogel lens body and the opaque color image Wherein the coating comprises an anchor layer of a polyanionic polymer and a layer of a hydrogel material, wherein the polyanionic polymer is one or more of acrylic acid, methacrylic acid, ethacrylic acid, and 2-acrylamidoglycolic acid , Or a homopolymer or copolymer of 2-methacrylamidoglycolic acid, wherein the hydrogel material is derived from a hydrophilic polymer material having a tetrahydroazinonium group and is A bond formed between a tetrahydroazine group is covalently attached to the anchor layer of the polyanionic polymer, wherein the colored contact lens in a fully hydrated state has after 7 cycles of manual friction A friction level of about 2 or lower.         The colored contact lens according to item 12 of the patent application scope, wherein the hydrogel lens is a non-silicone hydrogel lens body.         The colored contact lens according to item 13 of the patent application scope, wherein the non-silicone hydrogel lens body is composed of a polymer including at least 50% by mole of repeating units of at least one hydroxyl-containing vinyl monomer.     The colored contact lens according to item 14 of the scope of patent application, wherein the at least one hydroxyl-containing vinyl monomer is selected from the group consisting of: hydroxyethyl (meth) acrylate, 2-hydroxypropyl (Meth) acrylate, 3-hydroxypropyl (meth) acrylate, glycerol (meth) acrylate, N-2-hydroxyethyl (meth) acrylamide, N-2-hydroxypropyl ( (Meth) acrylamide, N-3-hydroxypropyl (meth) acrylamide, N, N-bis (hydroxyethyl) (meth) acrylamide, N-2,3-dihydroxypropyl (Meth) acrylamide, N -tris (hydroxymethyl) methyl (meth) acrylamide, vinyl alcohol, allyl alcohol, and combinations thereof. The colored contact lens according to item 13 of the application, wherein the non-silicone hydrogel lens body is composed of a non-silicone hydrogel material, and the non-silicone hydrogel material is a water-soluble, photochemically crosslinkable A crosslinked product of a polyvinyl alcohol prepolymer, the prepolymer comprising: at least 60% by mole of repeating units of vinyl alcohol; having repeating units of formula (I); and Wherein: R ₃ may be hydrogen or C ₁ -C ₆ alkyl; R ₄ is C ₁ -C ₆ alkylene divalent; R ₅ is hydrogen or C ₁ -C ₆ alkyl; R ₆ is or Ethylenically unsaturated groups, wherein q1 and q2 are independently zero or 1 and R ₇ and R ₈ are independently C ₂ -C ₈ alkylene divalent groups, and R ₉ is C ₂ -C ₈ Alkenyl.     The colored contact lens according to item 12 of the patent application scope, wherein the hydrogel lens is a silicone hydrogel lens body.         The colored contact lens according to any one of claims 12 to 17, wherein the polyanionic polymer is poly (acrylic acid) (PAA), poly (methacrylic acid) (PMAA), poly (acrylic-co- -Methacrylic acid) (pAA-pMAA), poly (ethylacrylic acid) (PEAA), poly (acrylic acid-co-ethylacrylic acid) (pAA-pEAA), poly (methacrylic acid-co-ethylacrylic acid) ( pMAA-pEAA), poly [2-acrylamidoglycolic acid], poly [2-methacrylamidoglycolic acid], or a combination thereof.     The colored contact lens according to any one of claims 12 to 17, wherein the water-soluble heat-crosslinkable polymer material comprises (i) from about 20% to about 95% by weight derived from Polyamidoamine-epichlorohydrin or poly (2- A first polymer chain of oxazoline-co-ethyleneimine) -epichlorohydrin, (ii) from about 5% to about 80% by weight of a hydrophilic moiety and / or a second polymer chain, wherein The hydrophilic portions are each derived from at least one first hydrophilicity enhancer, which is a monosaccharide containing a primary amine, a monosaccharide containing a secondary amine, a monosaccharide containing a carboxyl group, and a monosaccharide containing a thiol , Disaccharides containing primary amines, disaccharides containing secondary amines, disaccharides containing carboxyl groups, disaccharides containing thiols, oligosaccharides containing primary amines, oligosaccharides containing secondary amines, oligosaccharides containing carboxyl groups, A thiol-containing oligosaccharide, or a combination thereof, wherein the hydrophilic moieties are each supported by a tetrahydroacridium group on the polyamidoamine-epichlorohydrin and an amine of the first hydrophilicity enhancer Covalently attached to the first polymer chains by one or more covalent bonds formed between the amine, carboxyl, or thiol groups, wherein the second polymer chains are each derived from at least one Hydrophilicity enhancer of reactive functional group, the reactive functional group is selected from the group consisting of : A primary amine group, a secondary amine group, a carboxyl group, a thiol group, and combinations thereof, wherein the second polymer chains are supported by one or more tetrahydrogens each in the polyamidoamine-epichlorohydrin A covalent bond formed between an azenium group and an amine, carboxyl, or thiol group of the second hydrophilic enhancer to be covalently attached to the first polymer chains, and (iii ) Tetrahydroazinonium groups, which are part of the first polymer chains or are pendant or end groups covalently attached to the first polymer chains. The colored contact lens according to item 19 of the scope of patent application, wherein the water-soluble heat-crosslinkable polymer material comprises from about 5% to about 80% by weight of the second polymer chain, wherein the first Two hydrophilic enhancers: polyethylene glycol with a single amine, carboxyl or thiol group; polyethylene glycol with two terminal amine, carboxyl and / or thiol groups; one or Multi-arm polyethylene glycol with multiple amine, carboxyl, and / or thiol groups; polyethylene glycol dendrimers with one or more amine, carboxyl, and / or thiol groups; containing primary amines Polysaccharides containing secondary amines; polysaccharides containing carboxyl groups; hyaluronic acid; chondroitin sulfate; copolymers, which are polymerized products of a composition containing (1) about 60% by weight Or less one or more reactive vinyl monomers and (2) one or more non-reactive hydrophilic vinyl monomers, wherein the one or more reactive vinyl monomer systems have a carboxyl group, a primary amine group, Or secondary amine-based vinyl monomer, wherein the one or more non-reactive ethyl monomers The alkenyl monomer is selected from the group consisting of a vinyl monomer containing phosphinocholine, (meth) acrylamide, N, N-dimethyl (meth) acrylamide, N- Vinylpyrrolidone (NVP), N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, (formamidine Group) N, N-dimethylaminoethyl acrylate, N, N-dimethylaminopropyl (meth) acrylamide, glycerol (meth) acrylate, N-2-hydroxyethyl ( (Meth) acrylamide, N-2-hydroxypropyl (meth) acrylamide, N-3-hydroxypropyl (meth) acrylamide, N, N-bis (hydroxyethyl) (methyl) Acrylamide, N-2,3-dihydroxypropyl (meth) acrylamide, N -tris (hydroxymethyl) methyl (meth) acrylamide, N-methyl-3-methylene Methyl-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene Methyl-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, (meth) acrylic acid 2- hydroxyethyl (meth) acrylate having up to 1500 Daltons weight average molecular weight of C ₁ -C ₄ - alkoxy Polyethylene glycol (meth) acrylate, allyl alcohol, vinyl alcohol, and combinations thereof; or combinations thereof.     The colored contact lens according to item 20 of the patent application scope, wherein the colored contact lens has water from about 15% to about 80% by weight at room temperature (about 22 ° C to 28 ° C) when fully hydrated. Content and / or elastic modulus from about 0.2 MPa to about 1.5 MPa.         The colored contact lens according to item 21 of the patent application scope, wherein the coating has a thickness of at least 0.1 μm.